Patients with no known brain metastasis must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases OR
Active central nervous system (CNS) metastases; subjects must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) within 28 days prior to registration for protocol therapy to exclude brain metastases if symptomatic or without prior brain imaging
Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic; subjects with neurological symptoms should undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis, at the discretion of the treating physician
Subjects with known brain metastasis are excluded from this study; patients with suspected brain metastasis must have brain imaging (either magnetic resonance imaging [MRI] brain or computed tomography [CT] brain with contrast) prior to enrollment
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis. NOTE: Subjects with previously treated brain metastases may participate provided
Presence of untreated brain metastases; if patients have had previous treatment for the brain metastasis, an MRI or CT scan of the brain must confirm the stabilization of the brain metastasis for more than 2 months
Patients with more than 4 brain metastases on MRI brain or CT head
No evidence of CNS metastasis by MRI or CT of the brain performed within 28 days of enrollment
Known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis must have a CT or MRI performed within 4 weeks prior to randomization to specifically exclude the presence of radiographically-detected brain metastases
Active central nervous system (CNS) metastases\r\n* NOTE: Subjects who are symptomatic or have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) within 28 days prior to registration to exclude brain metastases\r\n* NOTE: A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for >= 2 weeks, are asymptomatic, and there is no evidence of progression on brain imaging (CT or MRI)
Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either magnetic resonance imaging [MRI] brain or CT brain with contrast) prior to enrollment
No active central nervous system (CNS) metastases; subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis within 28 days of registration; note: a subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
Brain metastases. Note: Patients with a history of brain metastases may be eligible, if an imaging scan with contrast enhancement not older than 4 weeks is able to exclude the existence of currently active brain metastasis
Active central nervous system (CNS) metastases; subjects with neurological symptoms should undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis, at the discretion of the treating physician\r\n* NOTE: A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
Patients with known brain metastases are not eligible; brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis; but, if brain imaging studies are performed, they must be negative for disease
Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system (CNS) is otherwise not required.
Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
The subject has current or previously treated brain metastasis or active leptomeningeal disease. Brain imaging is required during screening in all subjects to exclude the presence of unequivocal central nervous system disease.
History of or active CNS metastasis (brain, leptomeningeal or cord compression). Brain imaging studies are not required for eligibility if the subject has no neurologic signs or symptoms suggestive of brain metastasis. Subjects with neurological symptoms are recommended to undergo a head CT scan (with or without intravenous contrast) or brain MRI (with or without intravenous contrast) to exclude brain metastasis. If brain imaging studies are performed, they must be negative for CNS disease. Skull bone involvement without neurological impact by prostate cancer is allowed.
Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
Active central nervous system (CNS) metastases. Subjects must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration for protocol therapy to exclude brain metastases if symptomatic or without prior brain imaging
Patients with known brain metastases; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastases
Known brain metastasis; participants with brain metastasis can only be included if they were treated > 4 week prior to enrollment with radiation and the effects of treatment have resolved; subjects with treated brain metastases must have a post-treatment brain magnetic resonance imaging (MRI) showing no further progression of prior lesions and no new metastatic lesions; subjects will be ineligible if they have any ongoing symptoms from brain metastases or if there continues to be radiographic evidence of cerebral edema
Symptomatic or uncontrolled brain metastasis; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis; previously treated brain metastases will be allowed as long as the patient is neurologically stable and is off steroids and anticonvulsants
Symptomatic or uncontrolled brain metastasis; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis; previously treated brain metastases will be allowed as long as the patient is neurologically stable and is off steroids and anticonvulsants at the time of registration
Presence of untreated brain metastases; if patients have had previous treatment for brain metastasis, an MRI or CT scan of the brain must confirm the stabilization of the brain metastasis for more than 4 weeks
Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic; subjects with neurological symptoms should undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis, at the discretion of the treating physician
Known brain metastasis; patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis
Patients with known active brain metastases are excluded; head computed tomography (CT) is NOT routinely required prior to enrollment; patients with treated, asymptomatic brain metastasis will be eligible for enrollment
Subject has active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy (subjects must be off steroids). Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by brain MRI/CT.
Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for at least 21days prior to signing ICF). MRI of the brain (or CT scan w/contrast) is preferred for diagnosis.
Known central nervous system (CNS) or brain metastasis that are either symptomatic or untreated; Note: patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastasis\r\n* Note: patients with CNS metastases that have been treated and are stable without symptoms for >= 4 weeks after completion of treatment are eligible
Known brain metastasis; patients with neurological symptoms must undergo a computed tomography (CT) scan/MRI of the brain to exclude brain metastasis
No active brain metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 30 days prior to registration on protocol therapy. NOTE: A patient with prior brain metastasis are eligible if they have completed their radiation treatment for brain metastasis ?30 days prior to registration for protocol therapy, are off steroids, and are asymptomatic.
Active central nervous system (CNS) metastases; patients with neurological symptoms should undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis, at the discretion of the treating physician; NOTE: patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system (CNS) is otherwise not required.
Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic; subjects with neurological symptoms should undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis, at the discretion of the treating physician
No evidence of CNS disease by MRI or CT of the brain. Note: Prior brain metastasis which have been treated with definitive therapy are eligible.
Patients must have stage cT2-T4a N0 M0 disease; clinical T stage is based on the transurethral resection of the bladder tumor (TURBT) sample, exam under anesthesia and cross-sectional imaging studies; patients must undergo cystoscopy and TURBT as part of the staging procedure within 120 days prior to registration; to exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following:\r\n* Disease measuring at least 10 mm on cross-sectional imaging; bladder thickening on imaging, by itself, is not adequate\r\n* The presence of tumor-associated hydronephrosis
Patients with tumor morphology that predicts poor coverage of the majority of the tumor including bilateral thalamic involvement, or cysts that represent > 50% of cross-sectional areas of the pons. These subjects should be discussed with the study chairs.
Three or fewer total sites of active disease (at least one site of active disease to be treated on study must be confined to the abdomen or pelvis excluding liver and must be < 5 cm in greatest dimension as determined by pre-screening cross-sectional imaging)
No evidence of clinical progression, in the form of increased lesions on cross-sectional imaging, or new cancer-attributable symptoms or worsening of existing symptoms
Subjects must have metastatic disease detectable by either bone scan or cross sectional imaging by CT or magnetic resonance imaging (MRI) as per the PCWG3 guidelines
Cross-sectional imaging evidence of progression of recurrent/metastatic disease
Patients must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging
Dose-volume histogram data and cross-sectional imaging from previous radiation must be obtained; electronic dosimetry records in Digital Imaging and Communications in Medicine (DICOM) format from previous radiation are strongly preferred
< 90% solid component of tumor on screening cross-sectional imaging
MAIN STUDY COHORT INCLUSION CRITERIA: Presence of a solid enhancing cT1 renal mass (i.e. =< 7 cm) diagnosed on cross-sectional imaging
Documented recurrent disease: recurrent disease is defined either as radiological confirmation of the tumor, as an increase in tumor size of at least 25% based upon serial magnetic resonance (MR) images, or as development of a new site of disease\r\n* Tumor volume will be calculated using the sum of the largest cross-sectional perpendicular diameters of contrast-enhancing tumor, the sum of the largest cross-sectional perpendicular diameters of fluid attenuated inversion recovery (FLAIR) abnormality, or as worsened spectroscopic characteristics for any tumor type (development of >= 2 new voxels with choline to N-acetyl aspartate index [CNI] >= 3, or >= 25% increase in the sum of the CNI ratios within a group of previously abnormal voxels [where abnormal is defined as CNI ? 3])\r\n* Disease must be evaluable, but does not need to be measurable\r\n* The target site for SRS does not need to be located in a previously-irradiated area
Resectable disease at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the chest, abdomen, and pelvis (C/A/P)
Unresectable gallbladder cancer at the time of enrollment based on high-quality, preoperative, cross-sectional imaging of the C/A/P
Presence of visceral metastases (e.g. lung, liver) detectable on cross-sectional imaging or bone metastases requiring the use of opioid analgesic or focal radiation treatment at the time of study entry
Diagnostic quality, cross sectional imaging of the thorax within 28 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable.
Patients with locally advanced bladder cancer based on cross-sectional imaging (suspicion of extravesical disease or hydronephrosis)
Patients must have stage cT2-T4a N0 M0 disease; clinical T stage is based on the transurethral resection of bladder tumor (TURBT) sample and imaging studies; patients must undergo cystoscopy and TURBT as part of the staging procedure within 56 days prior to registration; to exclude non-bulky/low-risk tumors and ensure adequate tissue for assessment, subjects must have documented muscle invasion with at least one of the following:\r\n* Disease measuring at least 5 mm on cross-sectional imaging or by endoscopic assessment; bladder thickening on imaging without definable tumor is not adequate; pathology verification of >= 0.5 cm of viable tumor (longest diameter) from the biopsy sample and represented on the submitted slides is also acceptable\r\n* The presence of tumor-associated hydronephrosis
Histologically confirmed solid tumor malignancy with greater than 5 sites of metastatic disease detected on cross-sectional imaging
Evidence of metastatic disease or nodal disease outside the prostate on bone scan or cross-sectional imaging.
Either FDG-avid on FDG-PET or measurable disease by CT on cross sectional imaging: > 1.5 cm for nodal lesion, > 1.0 cm for extra nodal lesion.
Evidence of metastatic disease on cross sectional imaging or bone scan
MRI/CT must demonstrate measurable enhancing tumor of at least 1 cm^2 in cross-sectional area to allow assessment of radiographic response
Targeted index tumor(s) defined as intra pulmonary or pleural with a maximum size of 3.5 cm, measured in the longest cross sectional dimension.
Measurable disease on cross sectional imaging of at least 1 cm
Patients in the phase I portion must have:\r\n* Histologically confirmed diagnosis of metastatic, genitourinary solid tumor\r\n* Metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:\r\n** One evaluable site of disease \r\n** Or, appearance of one new bone lesion
Randomization within 112 days of completion of surgical \r\n* The primary region must be included on cross-sectional imaging (e.g. sinus/neck if arising from sinonasal primary; pelvis if genitourinary); radiographic changes considered nonspecific or possibly due to surgery or radiation are not considered evidence of disease
< 90% solid component on screening cross-sectional imaging
Clinical eligibility supported by central imaging real-time review\r\n* The presence of at least the following conventional magnetic resonance (MR) image characteristic:\r\n** Conventional MR\r\n*** Lesion quotient of < 0.3, where lesion quotient is defined as the proportional value of the maximum axial cross-sectional area of the transverse relaxation time (T2)-weighted defined lesion over the maximum axial cross-sectional area of the contrast-enhancing lesion on the longitudinal relaxation time (T1)-weighted post-gadolinium sequence on a comparable axial slice
Evidence of low-volume peritoneal disease defined by a peritoneal carcinomatosis index (PCI) =< 10 based on cross-sectional imaging and/or diagnostic laparoscopy findings
Cohort A only: Presence of at least three distinct metastatic lesions by standard imaging including whole body bone scan + cross-sectional imaging of the abdomen and pelvis obtained within 12 weeks prior to protocol scan
CT or MRI must demonstrate at least one lesion (primary or metastatic) present 1.5 cm or larger in any dimension on cross-sectional imaging (CT or MRI) obtained within 3 months of study enrollment
Completed radiographic evaluation with whole-body bone scan (99mTc-MDP or Na18F) and cross-sectional imaging (CT or magnetic resonance imaging [MRI]) of the abdomen and pelvis =< 42 days prior to study enrollment
No evidence of metastatic disease on conventional imaging, including a negative bone scan for skeletal metastasis and/or negative cross section imaging (MR or CT)
At least 1 measurable site of disease on cross-sectional imaging (CT/PET)
Subjects must have at least 1 lesion being targeted by TACE that is > 2 cm in the longest cross-sectional (axial plane) diameter
Cohort B only:- Presence of at least three distinct metastatic lesions by standard imaging including whole body bone scan + cross-sectional imaging of the abdomen and pelvis obtained within 12 weeks prior to protocol scan
Patients must have progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for PSA, measurable disease or non-measurable (bone) disease during treatment with ADT:\r\n* PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value >= 2.0 ng/mL\r\n* Measurable disease (by RECIST 1.1): > 20% increase in the sum of the longest diameters of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be more that 15 mm to be assessed for change in size\r\n* Non-measurable (bone) disease: The appearance of two or more new areas of uptake on bone scan (or NaF PET/CT) consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI)
Documented progressive metastatic (m)CRPC based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions\r\n* Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scan
Evidence of disease progression:\r\n* 2 or more new lesions on bone scan or\r\n* Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or\r\n* PSA progression consist of 3 PS rises, at least 2 weeks apart with the last value to be at least a 2 ng/ml
Metastatic castrate resistant prostate cancer, defined by progressive disease based on either rising PSA, new bone metastases, or progression of measurable disease on standard imaging, according to Prostate Cancer Working Group 2 (PCWG2) guidelines, despite androgen deprivation therapy
Documented progressive metastatic CRPC based on at least one of the following criteria:\r\n* Rise in PSA: a minimum of 3 rising levels, with an interval of at least 1 week between each determination; the last determination must have a value >= 1 ng/mL, obtained within 4 weeks of starting study drug\r\n* Measurable disease: new or progressive soft tissue disease on computerized tomography (CT) or magnetic resonance imaging (MRI) scans\r\n* Radionuclide bone scan: at least 2 new bone lesions, as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria
Progressive prostate cancer by either serum PSA levels, soft tissue or bone disease as defined by the PCWG2 criteria.
Castration-resistant prostate cancer requires the following criteria:\r\n* A castrate level of testosterone (< 50 ng/dL)\r\n* Prostate cancer progression on or since last treatment as documented by PSA rise or bone progression according to Prostate Cancer Working Group 2 (PCWG2) or soft tissue radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1\r\n* If on anti-androgen, will need to show no PSA decline after at least a 6 week withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks from last flutamide dose\r\n* Will require a 2 week washout period from last dose of ketoconazole, abiraterone acetate or radiation
Documented progressive metastatic CRPC based on at least one of the following criteria: \r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions or the appearance of new lesions\r\n* Documented appearance of new lesions by bone scan
Must have had disease progression while on abiraterone acetate alone or abiraterone acetate in combination with other investigational agents based on: \r\n* PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart and/or\r\n* Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or PCWG2 for patients with bone disease
Castrate-resistant prostate cancer, in the setting of castrate levels of testosterone (=< 50 ng/dL), defined as current or historical evidence of disease progression concomitant with surgical castration or androgen deprivation therapy (ADT), as demonstrated by two consecutive rises in prostate-specific androgen (PSA) OR new lesions on bone scan:\r\n* PSA progression will be defined as 2 rising PSA values compared to a reference value, measured at least 7 days apart and the second value is >= 2 ng/mL; it must be documented within 2 months of screening\r\n* Appearance of one or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression; it must be documented within 4 months of screening
Stage D0 disease with documented biochemical progression documented by rising PSA and no evidence of metastatic disease by physical examination, computed tomography (CT) scan or bone scan
Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:\r\n* PSA evidence for progressive prostate cancer which consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 1 week apart; if the confirmatory PSA value is less than the screening value, then an additional PSA value greater than #2 will be required to document progression of >= 1 week\r\n** PSA values to be obtained >= 1 week apart\r\n* Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\r\n* Bone disease progression defined by two or more new lesions on bone scan
Documented progressive metastatic castrate resistant prostate cancer (mCRPC) based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 1.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 1.0 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions\r\n* Progression of bone disease (evaluable disease) or two or more new bone lesions by bone scan
Patients must have progressive metastatic castration-resistant prostate cancer (mCRPC). There must be radiographic evidence of disease progression or biochemically (rising PSA levels on successive measurements) recurring disease despite adequate testosterone suppression.
Progression must be evidenced and documented by any of the following parameters:\r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination\r\n* Appearance of one or more new lesions consistent with prostate cancer on bone scan\r\n* New or growing lesions on computed tomography (CT) scan
Radiological confirmation of metastatic disease, or \r\n* Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone: \r\n** Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR \r\n** Prostate specific antigen (PSA) progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 1 ng/ml [prostate cancer working group 3 (PCWG3) PSA eligibility criteria]); if patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal; for patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal; the requirement for a 4-6 week withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months; for all other patients they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment
Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:\r\n* Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer\r\n* PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate Cancer Working Group 2 [PCWG2] PSA eligibility criteria); if patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal; for patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal; the requirement for a 4-6 week withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months; for all other patients, they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment
Histologically confirmed prostate adenocarcinoma without significant small- cell/neuroendocrine or other variant histologies, with rising PSA and/or radiographic progression in the setting of castration-level testosterone (< 50 ng/dL) indicating mCRPC. Patients must have either undergone surgical castration or continue on GnRH agonist/antagonist on the appropriate schedule throughout the study period.
Patients must have histologically confirmed progressive, metastatic castration resistant prostate adenocarcinoma by meeting ALL the following:\r\n* Pathology of prostate gland or metastatic disease must confirm the diagnosis of prostate adenocarcinoma; mixed histology with other variants including but not limited to small cell or neuroendocrine differentiation must be discussed with the study principal investigator (PI) \r\n* Metastasis must be documented by radiographic evidence\r\n* Castration resistance must be documented with surgical or medical castration with serum testosterone < 50 ng/d (< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to cycle 1, day 1 and must be continued throughout the study\r\n* Progression must be evidenced and documented by any of the following parameters\r\n** Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals; the minimal value to enter the study is 1.0 ng/ml or greater; the reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met, if values 3A or #4 are 1 ng/mL or higher (Prostate Cancer Working Group 3)\r\n** Appearance of one or more new lesions on bone scan\r\n** Progressive disease by RECIST 1.1
Progressive disease defined as one or more of the following three criteria (NOTE: Patients who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen): \r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 weeks between each determination. The PSA value at the screening visit should be >= 2 ng/mL \r\n* Soft tissue disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) \r\n* Bone disease progression defined by two or more new lesions on bone scan
Androgen independent prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression concomitant with surgical or medical castration, as demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:\r\n* PSA: two consecutive PSA values, at least 14 days apart, each >= 5.0 ng/mL and >= 50% above the minimum PSA observed during castration therapy or above the pre-treatment value if there was no response\r\n* Measurable disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response\r\n* Non-measurable disease: soft tissue disease: the appearance of 1 or more new lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n* Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression\r\n* Serum PSA >= 5.0 ng/mL\r\n* Castration levels of testosterone (< 50 ng/dL) achieved via medical or surgical castration; surgical castration must have occurred at least 3 months prior to registration; subjects who are not surgically castrate must be receiving medical castration therapy, have initiated such therapy at least 3 months prior to registration, and continue such therapy until the time of confirmed objective disease progression
Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:\r\n* Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR\r\n* PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2ng/ml [Prostate Cancer Working Group 2 (PCWG2) PSA eligibility criteria); if patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal; for patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal
Patients must have documented evidence of progressive disease as defined by any of the following: \r\n* PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >= 1.0 ng/mL.\r\n* New or increasing non-bone disease (RECIST).\r\n* Positive bone scan with 2 or more new lesions (Prostate Cancer Working Group 2 [PCWG2]).
Disease progression defined by one or more of the following three criteria:\r\n* PSA > 2.0 ng/mL and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart\r\n* Soft tissue progression as defined by RECIST v1.1 criteria\r\n* Bone disease progression as defined by Prostate Cancer Working Group 3 (PCWG3)
Documented progressive metastatic castration resistant prostate cancer (CRPC) based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL; Note: if confirmed rise is the only indication of progression, a minimal starting value of 1.0 ng/mL is acceptable, unless pure small-cell carcinoma\r\n* Soft-tissue progression based on new lesions or growth of existing soft tissue metastases\r\n* Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scan
Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions on bone scan.
Positive bone scan with 2 or more new lesions (PCWG3)
Subjects must have progressive disease at study entry defined as 1 or more of the following 3 criteria that occurred while the subject was on androgen deprivation therapy:\r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination; subjects who received an anti-androgen as part of their primary hormonal therapy must demonstrate progression after withdrawal; the PSA value at screening should be >= 2 ug/L (2 ng/mL)\r\n* Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\r\n* Bone disease progression defined by PCWG3 with two or more new lesions on bone scan\r\n* Note: for subjects enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan performed during prior therapy; if the comparison scan is not available, the baseline scan report must reference the previous scan to document progression
Bone disease progression is defined by PCWG2 as two or more new lesions on bone scan
Documented progressive mCRPC based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL\r\n* Progression of bidimensionally measurable soft tissue or nodal metastasis assessed within 42 days prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI)\r\n* Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan
Evidence of disease progression on ADT as evidenced by one of the following:\r\n* 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to Prostate Cancer Working Group 3 (PCWG3) criteria or Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies, OR\r\n* Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA level
Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone\r\ni. Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR\r\nii. PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2 ng/ml [Prostate Cancer Working Group (PCWG)2 PSA eligibility criteria]); if patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal; for patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal
Castration resistant disease defined as evidence of radiological and/or prostate specific antigen (PSA) progression despite castrate levels of testosterone (serum testosterone < 50 ng/dL [1.7 nmol/L]); for PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals; the first PSA value must be >= 4 (Prostate Cancer Working Group 2 [PCWG2] criteria)
Patients must have documented evidence of progressive disease as defined by any of the following: \r\n* Prostate-specific antigen (PSA) progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >= 1.0 ng/mL; \r\n* New or increasing non-bone disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1); \r\n* Positive bone scan with 2 or more new lesions (Prostate Cancer Clinical Trials Working Group [PCWG]3)
Known castration?resistant disease, defined according to Prostate Cancer Working Group 2 (PCWG2) criteria as:\r\n* Castrate serum testosterone level: =< 50 ng/dL (=< 1.7 nmol/L)\r\n* Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a gonadotropin-releasing hormone (GnRH) agonist in combination with an anti?androgen, must first progress through antiandrogen withdrawal prior to being eligible; the minimum timeframe to document failure of anti?androgen withdrawal will be four weeks\r\n* Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart; serum PSA at screening >= 2 ng/mL OR\r\n** Documented bone lesions by the appearance of two or more new lesions by bone scintigraphy OR\r\n** Bidimensionally?measureable soft tissue metastatic lesion assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
Castration resistant prostate cancer as defined by rising PSA when serum testosterone < 50 ng/ml (note: current testosterone results are not required if the potential subject has not missed any GnRH analogue/antagonist doses since their last result was received) AND one of the following:\r\n* PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart\r\n* Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors)\r\n* Progression of metastatic bone disease on bone scan with > 2 new lesions
Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and at least one of the following:\r\n* PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart\r\n* Evaluable disease progression by modified RECIST 1.1\r\n* Progression of metastatic bone disease on bone scan with > 2 new lesions
Progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) bone scan criteria or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during or after completing last therapy:\r\n* PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value >= 2.0 ng/mL\r\n* Measurable disease: >= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion\r\n* Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan (or NaF PET/CT) consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging [MRI])
Evidence of castration resistant disease in the setting of ongoing ADT (medical or surgical) as evidenced by one of the following:\r\n* Absolute rise in PSA of 2.0 ng/mL or an increase > 25% from the nadir, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA level, OR\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to RECIST 1.1 criteria, OR\r\n* At least 1 new bone scan lesion as compared to the most immediate prior radiologic studies
Key Eligibility Criteria:\n\n          -  Patients must have documented histological or cytological evidence of adenocarcinoma\n             of the prostate.\n\n          -  Must have progressive, metastatic castration-resistant prostate cancer (mCRPC). There\n             must be radiographic evidence of disease after primary treatment with surgery or\n             radiotherapy that has continued to progress radiographically or biochemically (rising\n             PSA levels on successive measurements) despite adequate androgen-deprivation therapy,\n             which is defined as having undergone bilateral surgical castration or continued\n             treatment on GnRH agonists or antagonists.\n\n          -  All patients in this trial must have been treated with enzalutamide.\n\n          -  Patients in Cohort 1 will not be allowed to have received prior chemotherapy; patients\n             in Cohort 2 must have received one (and not more) prior course of chemotherapy for\n             mCRPC.\n\n          -  Progression must be evidenced and documented by any of the following parameters:\n\n               -  PSA progression defined by a minimum of two rising PSA levels with an interval of\n                  ? 1 week between each determination\n\n               -  Appearance of one or more new lesions on bone scan\n\n               -  Progressive measurable disease by RECIST 1.1
Castration resistance will be defined as the development of disease progression, defined as one of the following:\r\n* Rising PSA x 2 values >= 2 weeks apart; minimum absolute PSA value 2 ng/mL\r\n* Radiographic progression, with at least 1 new site of metastasis\r\n* Symptomatic progression (ex: increase in pain despite stable imaging) AND despite ongoing luteinizing hormone-releasing hormone (LHRH) therapy OR testosterone level < 50
Radiographic progression of soft tissue disease by PCWG3-modified RECIST 1.1 criteria or bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression
Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration
Castration-resistant prostate cancer requires the following 3 criteria:\r\n* Progression after surgical castration or on gonadotrophin releasing hormone (GnRH) agonist or antagonist\r\n* A castrate level of testosterone (< 50 ng/dL)\r\n* Prostate cancer progression documented by PSA rise or bone progression according to Prostate Cancer Clinical Trials Working Group (PCWG2)
Castration resistant prostatic adenocarcinoma; subjects must have current or historical evidence of disease progression despite castrated level of testosterone (< 50 ng/dL) achieved by orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy; disease progression has to be demonstrated by PSA progression OR progression of measurable disease OR progression of non-measurable disease as defined below:\r\n* PSA: two consecutive rising PSA values, at least 7 days apart\r\n* Measurable disease: >= 20% increase in the sum of the longest diameters of all measurable lesions or the development of any new lesions; the change will be measured against the best response to castration therapy or against the pre-castration measurements if there was no response\r\n* Non-measurable disease: \r\n** Soft tissue disease: the appearance of 1 or more lesions, and/or equivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n** Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression
Castration-resistant based on a current or historical evidence of disease progression despite surgical or medical castration as demonstrated by one or more of the following:\r\n* Prostate-specific antigen (PSA) progression (defined as two consecutive PSA measurements at least 14 days apart >= 2.0 ng/ml and >= 50% above the minimum PSA during castration therapy or above pre-treatment value if no response)\r\n* Progression of measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) (>= 20% increase in the sum of the diameters of all target lesions or the development of any new lesions)\r\n* Progression of non-measureable disease based on imaging studies
Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ?1 week between each assessment where the PSA value at screening should be ?2 ng/mL; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression
Progression of bone disease according to PCWG3 criteria
Patients previously treated with neoadjuvant and/or adjuvant androgen deprivation (e.g. with radiation therapy) prior to the 6-month eligibility period are allowed, assuming they did not meet criteria for progression (defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir) while on treatment
Bone scan progression: at least two new lesions on bone scan, plus a rising PSA as described in (c) below.
A diagnosis of progressive castrate metastatic prostate cancer defined as one or more of the following three criteria: \r\n* Soft tissue progression defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 \r\n* Bone disease progression defined by Prostate Cancer Working Group 2 (PCWG2) with two or more new lesions on bone scan \r\n* Post-hormonal therapy rising PSA values from a hormone therapy nadir on >= 3 successive determinations at least two weeks apart, where the increase above the nadir is the greater of >= 2.0 ng/mL or a >= 10% change; (subjects with a rise in PSA but no evidence of metastases at any time by imaging studies will NOT be eligible)
Have a PSA or radiographic progression on enzalutamide; PSA progression is defined as two consecutive increases in PSA with the second level obtained at least 3 weeks after the first, and the second level of at least 0.5 ng/mL; soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or >= 2 new lesions on bone scan
Prostate cancer progression documented by prostate-specific antigen (PSA) according to the Prostate Cancer Clinical Trials Working Group (PCWG2) or radiographic progression of soft tissue according to modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) modified based on PCWG2, or radiographic progression of bone according to PCWG2
Prostate cancer progression since last prior therapy documented by prostate-specific antigen (PSA) according to Prostate Cancer Working Group 2 (PCWG2) or radiographic progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Evidence of disease progression on or after the most recent systemic treatment disease defined by the following criteria:\r\n* PSA: increasing PSA levels as defined by the Prostate Cancer Clinical Trials Working Group (PCWG2), determined by 2 consecutive measurements (compared to a baseline or nadir value); if the third measurement is below the second, then a fourth measurement must be greater than the second; the confirming third or fourth measurement must be >= 2 ng/mL; PSA progression must have occurred within 15 months of registration with at least 7 days between each PSA measurement; additionally the PSA progression as described above should have occurred during or after the most recent systemic treatment for prostate cancer\r\n* Measurable disease: >= 20% increase in the sum of the short axis diameter of all measurable lymph nodes or the development of any new measurable lymphadenopathy by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and PCWG2 criteria\r\n* Non-measurable disease:\r\n** Lymph node disease: appearance of 1 or more new lymphadenopathy, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response\r\n** Bone disease: appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response; increased uptake of pre-existing lesions on bone scan does not constitute progression
Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features with progressive metastatic disease based on any of the following:\r\n* Rise in prostate-specific antigen (PSA): minimum of 3 rising levels, with an interval of at least 1 week between each determination; the last determination must have a value >= 2 ng/mL, obtained within 4 weeks of starting study drug, or\r\n* Measurable disease: new or progressive soft tissue disease on computed tomography (CT) or magnetic resonance imaging (MRI) scans, or\r\n* Radionuclide bone scan: at least 2 new bone lesions, as defined by the Prostate Cancer Working Group 2 (PCWG2) criteria1
Histologically confirmed prostate cancer with progressive metastatic disease based on any of the following: i) a rise in PSA, ii) transaxial imaging, or iii) radionuclide bone scan\r\n* PSA - a minimum of 3 consecutive rising levels, with an interval of >= 1 week between each determination; the last determination must have a minimal value of >= 2 ng/mL and be determined within two weeks prior to enrollment\r\n* Measurable disease - patients showing new or progressive soft tissue masses on computed tomography (CT) or magnetic resonance imaging (MRI) scans as defined by the Prostate Cancer Working Group 2 (PCWG2) criteria\r\n* Radionuclide bone scan - at least two new metastatic lesions
Participants must have progressive disease as defined by one or more of the following:\r\n* Castrate resistant disease as defined by Prostate Cancer Working Group (PCWG)2; participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels >= 2 ng/ml (only the screening PSA needs to be >= 2 ng/ml) and testosterone levels < 50 ng/dL\r\n* Soft tissue progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\r\n* Bone disease progression defined by PCWG2 with two or more new lesions on bone scan
Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression
Bone disease progression as defined by Prostate Cancer Working Group 2 guidelines (at least 2 new lesions) on bone scan; or
Candidate for abiraterone therapy with documented evidence of metastatic castration-resistant prostate cancer. Metastatic status is defined as at least one documented metastatic lesion on either bone scan or CT/MRI scan. Castration resistant prostate cancer is defined as rising PSA or other signs of disease progression despite treatment with androgen deprivation therapy and the presence of a castrate level of testosterone (?50 ng/dL).
Serum PSA > 2.0 ng/mL; prostate cancer progression documented by PSA according to Prostate Cancer Working Group 2 (PCWG2) or radiographic progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Patients must have progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy; for patients enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan; if the comparison scan is not available, the baseline scan report must reference the previous scan to document progression\r\n* PSA progression defined by a minimum of two rising PSA levels with an interval of >= 1 week between each determination; patients who received an anti-androgen must have progression documented by a minimum of two rising PSA levels with an interval of >=1 week between each determination such that at least the second of these rises is >= 4 weeks since last flutamide, bicalutamide or nilutamide; the PSA value at the screening should be >= 2 ug/L (2 ng/mL)\r\n* Soft tissue disease progression defined by at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study)\r\n* Bone disease progression defined by PCWG2 with two or more new lesions on bone scan
Participants must have progressive disease as defined by either:\r\n* Castrate resistant disease as defined by Prostate Cancer Working Group (PCWG); participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels >= 2 ng/ml (only the screening PSA needs to be >= 2 ng/ml) and testosterone levels < 50 ng/dL, OR\r\n* Soft tissue progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, OR\r\n* Bone disease progression defined by PCWG2 with two or more new lesions on bone scan
Evidence of disease progression on ADT as evidenced by one of the following:\r\n* Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of >= 1 week between each PSA level, OR\r\n* 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR\r\n* Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to modified Prostate Cancer Working Group 2 (PCWG2) criteria or modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies
Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:\r\n* Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR\r\n* PSA progression defined by sequence of rising values separated by > 1 week (2 separate increasing values over a minimum of 2 ng/ml [Prostate Cancer Clinical Trials Working Group (PCWG2) PSA eligibility criteria]); if patient has been on flutamide, PSA progression is documented 4 weeks or more after withdrawal; for patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal; the requirement for a 4-6 week withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months; for all other patients they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment
Progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) bone scan criteria or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during or after completing last therapy:\r\n* PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value >= 2.0 ng/mL\r\n* Measurable disease: >= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion\r\n* Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging [MRI])
Progressive disease at study entry defined by PSA and/or radiographic criteria according to the Prostate Cancer Working Group 2 (PCWG2)
Must have metastatic, progressive, castrate resistant prostate cancer (CRPC); there must be radiographic evidence of disease after primary treatment with surgery or radiotherapy that has continued to progress radiographically or biochemically (rising prostate specific antigen [PSA] levels on successive measurements) despite adequate androgen-deprivation therapy, which is defined as having undergone bilateral surgical castration or continued treatment on gonadotropin-releasing hormone (GnRH) agonists or antagonists\r\n* Progression must be evidenced and documented by any of the following parameters:\r\n** Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals\r\n** Appearance of one or more new lesions on bone scan\r\n** Progressive measurable disease by RECIST 1.1\r\n* The use of androgen receptor inhibitors is not required prior to study entry; for those patients receiving an anti-androgen agent (flutamide, bicalutamide, or nilutamide), for at least 6 consecutive months immediately prior to study entry, and are entering the trial due to a rise in PSA, they must demonstrate a continued rise in PSA within 4 weeks after stopping flutamide and within 6 weeks after stopping bicalutamide or nilutamide; flutamide, nilutamide and bicalutamide disease progression requirements only apply to patients who have been on these drugs for at least the prior 6 months
Have progressive metastatic castration-resistant prostate cancer, on androgen-deprivation therapy, based on at least one of the following criteria:\r\n* PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval with a minimum PSA of 2 ng/mL\r\n* Progression of bidimensionally measurable soft tissue (nodal metastasis) assessed within one month prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis\r\n* Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan
Histologically or cytologically confirmed prostate cancer with progressive disease defined as either:\r\n* 2 or more new lesions on bone scan or\r\n* Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria or\r\n* Rising PSA: PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart
Must have shown clinical characteristics of acquired resistance to enzalutamide or apalutamide defined as: decline in serum PSA ?50% compared to baseline serum levels by week 12 (±4 weeks) of enzalutamide or apalutamide treatment and before disease progression by PCWG3 PSA criteria, OR disease progression by PCWG3 radiographic criteria. (Part 2 only) Parts 1 and 2:
Bone disease progression defined by 2 or more new lesions on 2 consecutive bone scans in the absence of falling PSA
Evidence of disease progression (PSA progression, or radiographic/clinical progression [Prostate Cancer Working Group (PCWG2)])\r\n* PSA progression is defined as at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value >= 2.0 ng/mL\r\n* Radiographic progression is defined for soft tissue lesions using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, i.e an increase greater than 20% in the sum of the longest diameter of all target lesions based on the smallest sum longest diameter since treatment started or the appearance of one of more new lesions with a confirmatory scan 6 or more weeks later; radiographic progression will be defined for bone lesions as the appearance of two new lesions with a confirmatory scan performed 6 or more weeks later that shows at least 2 or more additional new lesions
Documented progression on (a) at least one prior hormone treatment, which must have incorporated LH-RH agonist therapy AND (b) at least one chemotherapy regimen, which must have been taxane based; progression may be demonstrated by ) or radiologic criteria (defined by radiologic documentation of a new lesion or a >= 20% increase in the sum of the diameters of previously noted measurable lesions) or by PSA (defined by a 25% increase in the PSA from its most recent treatment nadir, confirmed with a second measurement at least 4 weeks later) only if accompanied by new or worsening symptoms (pain progression)
Prostate cancer progression documented by PSA and/or radiographic progression according to prostate cancer working group 2 (PCWG2).
Patients must have a histologically confirmed diagnosis of adenocarcinoma of the prostate that is hormone refractory and with evidence of progressive metastatic disease following docetaxel treatment by any of the following:\r\n* Increased serum prostate-specific antigen (PSA) levels confirmed by 3 consecutive PSA measurements (at least 2 weeks apart)\r\n* Progression of bidimensionally measurable soft tissue (nodal) metastasis by computed tomography (CT) scan or magnetic resonance imaging (MRI) within the past 4 weeks and/or\r\n* Progression of bone disease by at least two new bone lesions on bone scan confirmed by a second bone scan
Appearance of 2 or more new bone lesions according to Prostate Cancer Working Group 2 (PCWG2).
Progressive disease as demonstrated by a rising PSA (at least two determinations) prior to study entry, and/or radiographic evidence of tumor progression in soft tissue according to modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria or identification of new lesions by bone scan (i.e., >= 2 new lesions)
Other second-generation investigational anti-androgen/androgen-receptor targeted therapies, including apalutamide (ARN-509); primary resistance will be defined as:\r\n* No PSA decline\r\n* PSA decline less than 50% after 12 weeks of enzalutamide therapy\r\n* PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria), after initial response to therapy\r\n* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide treatment\r\n* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting enzalutamide treatment
Progressive disease while receiving hormonal therapy or after surgical castration documented by at least one of the following: (1) increase in measurable disease per RECIST 1.1; (2) appearance of new lesions on bone scan consistent with progressive prostate cancer (>= 2 new lesions on bone scans if this is the only measure of progressive disease (PD); (3) rising PSA defined as 2 sequential increases above a previous lowest reference value; each value must be obtained at least 1 week apart
Patients must have evidence of disease progression during current or prior therapy with abiraterone with either:\r\n* Biochemical progression as defined as rising PSA by Prostate Cancer Clinical Trials Working Group (PCWG2) from a nadir or baseline (whichever was lowest) confirmed on a second determination at least 1 week later that must be higher than the first and must have reached >=2 ng/ml (if no other evidence of progression); or\r\n* New metastases on bone scan (at least 2); or\r\n* Progression of measurable disease on computed tomography (CT) scan by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Development of liver metastases in the absence of PSA progression as defined by PCWG2
Bone disease progression defined by PCWG2 criteria (two or more new lesions on bone scan compared with prior scan)
Has progressive disease at time of enrollment defined as one or more of the following criteria: PSA progression defined by PCWG2 criteria or soft tissue disease progression defined by RECIST 1.1 or bone disease progression defined by PCWG2 criteria Able to swallow and retain orally administered medication.
Metastatic castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following:\r\n* Prostate specific antigen (PSA) level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart\r\n* Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors) \r\n* Progression of metastatic bone disease on bone scan with > 2 new lesions
Prostate cancer progression documented by 1 of the following: PSA progression according to Prostate Cancer Working Group 2 (PCWG2) criteria, radiographic progression by modified Response Evaluation Criteria in Solid Tumors (RECIST) or bone scan
Inclusion Criteria:\n\n        Men, ?18years of age with documented asymptomatic or minimally symptomatic metastatic\n        castration-resistant prostate cancer.\n\n        Documented progressive disease post surgical castration or during androgen suppression\n        therapy, or during complete androgen blockade therapy and withdrawal. Documented by either\n        criterion a (Radiological progression), OR criterion b (PSA progression).\n\n          1. Radiological progression defined as any new/enlarging bone metastases or new/enlarging\n             lymph node disease, consistent with prostate cancer.\n\n             OR\n\n          2. PSA progression defined by sequence of rising values separated by > 1 week (2 separate\n             increasing values) over a threshold minimum of 2.0 ng/ml. (PCWG2 PSA eligibility\n             criteria).\n\n        Chemotherapy naïve and Vaccinia-experienced (previous smallpox vaccination). Currently\n        using a GnRH agonist or antagonist (unless surgically castrated).\n\n        Exclusion Criteria:\n\n        Cancer-related pain requiring scheduled opioid narcotics for control (as needed, ? 2x per\n        week is allowed).\n\n        Metastasis to organ systems other than lymph nodes and/or bone. Estimated PSA doubling time\n        of <1 month as established within 6 months of the anticipated first dose of vaccine or\n        placebo.\n\n        Concurrent or prior Provenge (sipuleucel-T) immunotherapy for prostate cancer. Receipt of\n        an investigational agent within 30 days (or 60 days for an antibody-based therapy) of the\n        first planned dose of PROSTVAC-V/F.\n\n        History of prior malignancies other than prostate cancer within the past 3 years, excluding\n        successfully resected basal or squamous cell carcinoma of the skin.\n\n        Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or\n        hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or\n        myocardial infarction (current or within the past 6 months) Confirmed positive for HIV,\n        hepatitis B, and /or hepatitis C. Immunodeficiency or splenectomy. History of or active\n        autoimmune disease, persons with vitiligo are not excluded. Diabetics are not excluded if\n        the condition is well controlled.\n\n        History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that\n        disrupts the epidermis.
Have documented disease progression while receiving or following hormonal therapy as determined by increasing Serum Prostate Specific Antigen (PSA) level, Radiological Progression, or ?2 new bone lesions
Documented progressive metastatic CRPC based on at least one of the following criteria:\r\n* PSA progressive defined as 25% increased over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL\r\n* Soft-tissue progression defined as an increase >= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions\r\n* Progression of bone disease (evaluable disease) or (new bone lesion[s]) by bone scan
Castration-resistant disease according to PCWG2 criteria
Progressive disease manifest by either;\r\n* Imaging modalities:\r\n** New osseous lesions on bone imaging (bone scintigraphy or sodium fluoride [NaF] PET scan) and/or\r\n** An increase in measurable soft tissue disease, or the appearance of new sites of disease OR\r\n* A minimum of three rising prostate-specific antigen (PSA) values from a baseline that are obtained 1 week or more apart, or 2 or more weeks apart\r\n* PSA changes: \r\n** Androgen-independent, minimum number (No.) of determinations 3, interval >= 1 week, percentage increase over 25%\r\n** Androgen-independent, minimum No. of determinations 2, interval >= 2 week, percentage increase over 25%
Documented metastatic prostate cancer progression as assessed by the treating oncologist with either one or both of the following:\r\n* Rising PSA over a minimum 1-week interval\r\n* Radiographic progression in soft tissue and/or bone
Visible lesions by either computed tomography (CT), bone scan or magnetic resonance imaging (MRI) consistent with metastatic disease\r\n* Metastatic progressive disease\r\n* Imaging modalities:\r\n** Bone scan: new osseous lesion and/or\r\n** MRI or CT: an increase in measurable soft tissue disease or the appearance of new sites of disease OR\r\n* Prostate specific antigen (PSA) changes showing androgen independent, minimum number of determinations: 3; interval >= 1 week; percentage increase over range of values: 25%\r\n* PSA changes showing androgen independent, minimum number of determinations: 2; interval >= 2 week; percentage increase over range of values: 25%
- Castration-resistant disease as defined by PCWG2 criteria
Patients must have progressive prostate cancer as indicated by either PSA progression (PSA progression is defined as two consecutively rising PSAs above the nadir post-definitive therapy and an absolute value greater than 1.0 ng/mL separated by at least 2 weeks) or radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or Prostate Cancer Working Group 3 (PCWG3).
No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (sodium fluoride [NaF] positron emission tomography [PET]/CT is an acceptable substitute)\r\n* Equivocal bone scan findings are allowed if plain films (or CT or magnetic resonance imaging [MRI]) are negative for metastasis
Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site
For the purpose of this study metastatic disease is defined as one or more of the following:\r\n* Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor; skip lesions in the same bone as the primary tumor do not constitute metastatic disease; skip lesions in an adjacent bone are considered bone metastases; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed\r\n* Contralateral pleural effusion and/or contralateral pleural nodules\r\n* Distant lymph node involvement\r\n* Patients with pulmonary nodules are considered to have metastatic disease if the patient has:\r\n** Solitary nodule >= 0.5 cm or multiple nodules of >= 0.3 cm unless lesion is biopsied and negative for tumor\r\n** Patients with solitary nodule < 0.5 cm or multiple nodules < 0.3 cm are not considered to have lung metastasis unless biopsy documents tumor\r\n* Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on hematoxylin and eosin (H&E) stains; in the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse-transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study\r\n** This study requires bilateral bone marrow biopsies at study entry; the suggested approach for patients with large pelvic tumors in which a posterior iliac crest bone marrow biopsy would track through the tumor is to instead undergo 2 marrow biopsies on the contralateral side (either 2 posterior biopsies or one posterior and one anterior biopsy)\r\n* Bone metastasis: This study utilizes whole body FDG-PET scans to screen patients for bone metastases; areas suspicious for bone metastasis based on FDG-PET scans require confirmatory anatomic imaging with either MRI or computed tomography (CT) (whole body FDG-PET/CT or FDG-PET/magnetic resonance [MR] scan acceptable); whole body technetium bone scans may be performed at the discretion of the investigator and are not required; for patients without other sites of metastatic disease whose sole metastatic site to qualify for study entry is a single area suspicious for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic imaging evidence of an associated soft tissue mass at that site is required for study entry
Metastases with indistinct borders making targeting not feasible\r\n* NOTE: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician’s judgment will be required
Bone scan as clinically indicated within 90 days prior to registration
Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer.
Exercise Coordination Centre (ECC) review and approval of subject's screening bone scan/ areas with bone metastases.
Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
Bone metastases
Subjects with chronic conditions associated with non-malignant abnormal bone growth (e.g., Paget’s disease of bone)
Bone metastases
Bone metastases as manifested by one or more lesions on a bone scan performed within 2 months of screening
Other bone and soft tissue sarcomas cohort only: Subjects with dedifferentiated chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone, undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of bone must have received at least one prior line of therapy unless no standard first-line therapy exists in which case enrollment as initial therapy is allowed.
Cohort B1\r\n* Newly diagnosed low-volume metastatic disease with either:\r\n** Bone metastases as documented by radionuclide bone scan amenable to treatment with a maximum of 3 radiation isocenters* (note: a patient will be considered eligible if entering the study with a positive positron emission tomography (PET) scan without restriction to the number of isocenters and otherwise meets eligibility requirements) And/Or\r\n** Retroperitoneal nodes up to the level of the renal hilum with/without pelvic nodal metastasis < 1.5 cm in the short axis OR
Patients must have measurable disease by RECIST v1.1, or evaluable disease with bone metastases demonstrated by Tc99 bone scan; patients with bone metastases only are allowed (NOTE: nodes >= 1.5 cm (not >= 2 cm) in the short axis are considered measurable, per The Prostate Cancer Working Group 3 [PCWG3])
Combo C : Hypocalcemia, clinically significant bone disease or recent bone fracture (within 12 weeks prior study entry)
Bone only patients during expansion/efficacy portion.
No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase
Paget’s disease of bone
At least 1 osteolytic bone metastases must be present
Localized pain resulting from no more than two sites total of metastatic disease in the bone and/or benign bone tumors (Benign Bone Tumors are restricted to Europe and Canada only)
Subjects must have at least 1 bone metastasis of any size on imaging
No evidence of metastasis on bone scan within 120 days prior to registration
Subjects with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan.
Metastatic disease as defined by two or more bone metastases confirmed by bone scintigraphy or radiographic soft tissue metastasis
Confirmed bone metastases on imaging
Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
The patient should not have direct evidence of regional or distant metastases after appropriate staging studies, including no distant metastases (M0) on bone scan within 90 days of study enrollment; equivocal bone scan findings are allowed if plain films are negative for metastasis; positron emission tomography (PET) or prostate specific membrane antigen (PSMA) scans can be performed instead of a bone scan
Bone-predominant metastatic castration resistant prostate cancer (CRPC): at least two skeletal metastases on bone scan with no lung, liver, and/or brain metastasis (lymph node metastasis is allowed)
No evidence of bone metastases (M0) on bone scan, only for PSA > 20 or Gleason >= 8, (sodium fluoride [NaF] positron emission tomography [PET]/CT is an acceptable substitute) performed no more than 120 days prior to registration; equivocal bone scan findings are allowed if plain films and/or MRI are negative for definite metastases
Bone scan completed within 90 days
No evidence of bone metastases (M0) on bone scan within 90 days prior to registration
Subjects with pathologic long-bone fractures
Paget’s disease of bone
No evidence of bone metastases (M0) on bone scan\r\n* Patients with intermediate risk factors only do not require a bone scan, but these studies may be obtained at the discretion of the treating physician\r\n* Patients with any high risk factors are required to undergo a bone scan; it is recommended that the duration between these scans and study registration be less than 60 days, but if the time period is > 60 days and the opinion of the clinician is that repeat studies would offer limited benefit, then these studies do not need to be repeated\r\n* Equivocal bone scan findings are allowed if additional imaging (e.g. plain film x-rays, or CT) does not confirm metastasis
Metastatic disease documented by CT/MRI or bone scan (not older than 28 days at enrollment) revealing at least one metastatic lymph-node, visceral metastasis and/or bone metastasis
Previously administered chemotherapy or 223Ra-therapy within the context of diffuse bone or bone-marrow involvement (i.e. \superscan\ defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases)
Patients who are suffering from symptoms of bone metastases
Patient whose targeted (most painful) tumors are on bone and bone-lesion interface is deeper than 1cm from the skin.
Presence of metastatic disease on bone or computed tomography (CT) scan \r\n* Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)\r\n* Bone disease on bone scan
Oligometastatic prostate cancer patients who have not received primary therapy are eligible; (oligometastatic disease is defined as a patient with ? 3 metastatic bone lesions on the bone scan or tissue metastasis)
Subjects must have a negative bone scan
The subject must have clear evidence of metastases to bone on isotope bone scan at screening, with or without soft tissue metastases; in subjects with bone-only disease, at least two bone lesions must be evident on baseline imaging that are not within a previously irradiated field
Metastatic disease by bone scan
Soft tissue components of bone metastases >= 1.0 cm in longest axis\r\n* Soft tissue components of bone metastases < 1.0 cm that have been stable for > 6 months (must not have enlarged > 5 mm) are permitted
Multiple bone metastases within 12 weeks prior to study drug
Bone disease progression defined by ?2 new lesions on bone scan at Screening, or ?28 days of C1D1
Bone scan or positron emission tomography (PET) scan; required only if alkaline phosphatase (ALP) is ?2 x upper limit of normal (ULN) and/or there are symptoms of metastatic bone disease. A confirmatory imaging study is required if the results from the bone scan are questionable
Alkaline phosphatase =< 2.5 x IULN for patients without bone metastases and =< 5.0 x IULN for patients with bone metastases
Bone-limited and exclusively metastases.
Patients with either measurable disease as defined by RECIST criteria or bone only disease are eligible; Note: those patients with both non-measurable disease and bone metastases are eligible\r\n* Non-measurable bone only disease: Non-measurable bone only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft-tissue component, or mixed lytic-blastic bone lesions without a measurable soft-tissue component\r\n* Lytic bone lesions, with an identifiable soft tissue component, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), can be considered as measurable lesions if the soft tissue component otherwise meets the definition of measurability previously described
Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by CT/magnetic resonance imaging (MRI). Presence of metastases in soft tissue (skin, subcutaneous, muscle, fat, lymph nodes)and/or visceral metastases is allowed.
Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)
Progression of bone disease (evaluable disease) or (new bone lesion(s)) by bone scan.
No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration\r\n* Equivocal bone scan findings are allowed if plain films and/or MRI are negative for metastasis
Bone-directed radiotherapy to pelvic region for ease of pain from painful bone metastases is allowed up to 14 days before
Progression of bone disease (evaluable disease) (new bone lesion(s)) by bone scan.
Evidence of metastatic disease in bone on bone scan, CT scan, and/or by MRI at any time following the initial diagnosis of prostate cancer
No evidence of bone metastases (M0) on bone scan within the past 60 days prior to registration        \r\n* Bone scan not required for patients enrolled with a single intermediate-risk factor only but this scan may be obtained at the discretion of the treating physician; patients with 2 or 3 risk factors will require a negative bone scan for eligibility\r\n* Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis
Patients with Paget's disease of the bone
No distant metastases (M0) on bone scan or NaF PET/CT within 14 weeks prior to registration; equivocal bone scan findings are allowed if the physician determines that distant metastases are unlikely based on clinical judgment
Presence of at least one metastatic bone lesion(s); patients with non-measurable bone-only disease are allowed
Presence of bone metastatic disease as assessed by at least two lesions on whole body metastable technetium-methylene diphosphonate (99mTc-MDP) bone scintigraphy;
Bone metastases
Stage IV breast cancer with metastases to the bone and/or bone marrow
Pathological or radiographically confirmation of metastases to the bone and/or bone marrow; (the definition of radiologic diagnosis of bone metastasis is based on typical and highly reliable imaging findings in studies such as bone scan [new or multiple TC99m positive lesions], PET/computed tomography [CT] [new or multiple FRG positive lesions], and magnetic resonance imaging [MRI] [typical T1w replacement, T2w positive and T1 plus contrast media positive] for bone metastasis with 2 or more lesions; if the bone metastasis is highly suspected or not well defined by imaging, bone biopsy is necessary for confirmation)
Bone-only disease and/or disease that cannot be biopsied.
Symptomatic bone metastases
Current, untreated pathologic long-bone fractures or imminent pathologic long-bone fracture (cortical erosion on radiography > 50%)
Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis.
Multiple skeletal metastases (?2 hot spots) on bone scan
Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
Two or more skeletal metastases (? 2 hot spots) on bone scintigraphy within 8 weeks of randomization
Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
COHORT A: The subject must have a history or presence of =< 10 bony metastatic lesions \r\n* Note: bone metastases (mets) that are not clearly identified on bone imaging, but are biopsy proven are allowed
Patients currently receiving bone loss prevention treatment with bone-sparing agents must be on stable doses for at least 4 weeks prior to randomization
Patients with progressive, locally recurrent, or metastatic osteosarcoma (i.e. high-risk only) with no standard curative options available with at least one indicator lesion avid on 99mTc-MDP scan or a Sodium Fluoride (Na F) Bone PET scan will be eligible. In addition, subjects with extremely rare bone forming osteosarcoma-like tumors that behave like osteosarcoma phenotypically and are clinically treated like osteosarcoma (eg. Malignant Fibrous Histiocytoma of Bone or malignant transformation of giant cell tumor of bone) may be included if they satisfy all of the inclusion criteria.
Indicator lesion that has uptake of 99mTc-MDP on bone scan or a Sodium Fluoride ( Na F) Bone PET scan and can be subjected to quantitative assessment by this scans and possibly other means.
99mTc-MDP bone scan with no significant uptake (i.e. \nothing\ for a bone-seeking isotope to target/ i.e. indicator lesion that would be expected to have the bone-seeking targeted uptake of 223-radium dichloride).
Patients with bone metastases only
Known brain metastasis or evidence of metastatic disease by computed tomography (CT) scan, physical exam, or bone scan within 4 weeks of registration\r\n* Patients with equivocal uptake on a bone scan that in the clinician's opinion do not definitively constitute metastatic disease are eligible
Patients with \anaplastic\ features are eligible for this trial as defined by at least one of the following: a) any of the following metastatic presentations: exclusive visceral metastases, radiographically predominant lytic bone metastases identified by plain X-ray or CT scan, bulky (> 5 cm in longest dimension) lymphadenopathy or high-grade (Gleason > 8) tumor mass in the prostate/pelvis; b) low PSA (=< 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases; c) elevated serum lactate dehydrogenase (LDH) (>= 2 x ULN) or elevated serum carcinoembryonic antigen (CEA) (>= 2 x ULN) in the absence of other etiologies; d) short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy
1 to 3 bone metastatic sites (metastatic lesions in the same bone that are within 3 cm of each other are considered as one site)
Negative bone scan within 6 months prior to enrollment to rule out possibility of metastases;
Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
The subject must be willing to undergo sequential biopsy of bone or bone metastases
Patients with bone metastases only
Patients with either skeletal pain or alkaline phosphatase that is > ULN must have a bone scan showing they do not have metastatic disease; suspicious findings on bone scan must be confirmed as benign by x-ray, magnetic resonance imaging (MRI), or biopsy
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Metastatic prostate cancer to the bone as documented by positive bone scan imaging
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Presence of 1 or more bone metastasis
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Bone metastases and one of the following:
Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
Bisphosphonates or Zometa for bone metastases
Patients who have a solitary bone metastasis that has been irradiated are not eligible.
2 or more bone metastases demonstrated on bone scintigraphy
Patients who are suffering from symptoms of bone metastases or multiple myeloma bone lesions:
Children with any cancer diagnosis except for bone tumors or have bone metastasis
Receiving bone modifying agents for bone pain associated with metastatic disease or other chronic conditions
Have lesion or metastasis of bone
Solid organ malignancy with documented bone metastasis by imaging
Malignancy with bone instability
History of bone fractures
Measurable disease per RECIST 1.1 or bone-only disease with lytic component. Patients with bone-only metastatic cancer must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by computerized tomography (CT) or magnetic resonance imaging (MRI). Patients with bone-only disease without a lytic component (ie, blastic-only metastasis) are not eligible.
Bone scan without evidence of skeletal metastases
Skeletal x-ray film or MRI confirmation of absent skeletal metastases if bone scan findings are equivocal
Biopsy proven or clinically obvious documented bone metastases from breast cancer (with the majority of the disease burden in the bone)
Patient has known bone metastases
No evidence of metastatic disease on conventional imaging, including a negative bone scan for skeletal metastasis and negative contrast-enhanced CT
Bone scan findings characteristic for metastatic prostate carcinoma
Untreated/unstabilized pathologic long bone fractures
?2 new metastases on transaxial imaging or radionuclide bone scan
Patients must have measurable disease by RECIST v.1.1 or bone disease as their only site of disease (with bone lesions confirmed by CT, MRI or bone X-ray).
No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (PET/CT is an acceptable substitute). Equivocal bone scan findings are allowed if bone CT or MRI of hot spots are negative for metastasis