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).