PSA at screening must be ?2 µg/L.
Last PSA value should have increase of ? 25% of the first PSA value and an absolute increase of ?2 ng/mL over the first PSA value
Prostate- specific antigen (PSA) Progression: An elevated PSA ?2 ng/ml that has risen serially on at least two occasions, each at least one week apart (PSA1 < PSA2 < PSA3). If the 3rd PSA value is less than the 2nd PSA value, than an additional test for rising PSA is required to document progression. (For the purposes of the nomogram calculator, the last PSA value recorded prior to initiation of the intervention will be considered the baseline PSA)
Progressive disease during (or within 4 weeks of completion) with abiraterone, enzalutamide, and/or androgen receptor antagonist ARN-509 (ARN-509) based on any one of the following:\r\n* For patients with measurable disease, progression by the Response Evaluation Criteria in Solid Tumors (RECIST)\r\n* PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression for the purposes of eligibility\r\n* Radionuclide bone scan: at least two new foci consistent with metastatic lesions
PSA relapse within 4 years of prostatectomy defined by persistently detectable or rising PSA after surgery
Confirmation of detectable PSA after radical prostatectomy, OR presence of extracapsular extension, seminal vesicle invasion or positive surgical margin if postoperative PSA is undetectable (adjuvant RT)
Biochemical progression (rising PSA) after medical or surgical castration
Rising PSA as defined above and either:
Evidence of rising PSA, on 2 separate occasions, at least one week apart; baseline PSA must be >= 0.2 ng/mL at the time of screening; radiographic evidence of disease is not allowed
Patients must be withdrawn from abiraterone for >= 2 weeks and have documented PSA increase after the 2 week withdrawal period
Patients with mCRC must have measurable PSA above normal limits per local ranges.
No metastatic disease as per NCCN guidelines (www.nccn.org) - Bone scan indicated to r/o metastatic disease if clinical T1 and PSA > 20 or T2 and PSA > 10
Patient must have evidence of biochemical failure after primary therapy and subsequent progression; biochemical failure is declared when the PSA reaches a threshold value after primary treatment and it differs for radical prostatectomy or radiation therapy\r\n* For radical prostatectomy the threshold for this study is PSA >= 0.2 ng/mL\r\n* For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA achieved post radiation with or without hormone therapy (2006 Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] Consensus definition)\r\n* PSA progression requires a PSA rise above the threshold measured at any time point since the threshold was reached
History of progressive disease after androgen deprivation, defined by one OR both of the following:\r\n* Objective radiographic progression defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria\r\n* Prostate-specific antigen (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 not greater than the screening PSA value, then an additional test for rising PSA will be required to document progression
Asymptomatic mCSPC patients with > 75% PSA decline after 12 weeks of run in period with ADT, abiraterone plus prednisone
Progressive disease by PSA or imaging after most recent prior therapy. PSA ?1 ng/mL, if a confirmed rise in PSA is the only indication of progression. Progression by PSA requires rising PSA over a previous reference value by at least 2 measurements obtained ? 1 week apart.
Two rising PSA values separated by at least 1 week, one showing a rise of at least 0.5 ng/mL and one confirmatory value not showing a decline, while on abiraterone therapy.
Patients must have a rising PSA as confirmed by 3 values a minimum of 1 week apart over at least a 1 month period of time
PSA relapse within 4 years of prostatectomy defined by persistently detectable or rising PSA after surgery
PSA failure after definitive radiation as defined by the Phoenix criteria (PSA elevation at least 2 ng/dL above post-radiotherapy nadir)
A minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be ? 2 ?g/L (2 ng/mL) if qualifying solely by PSA progression.
Have received at least 4 cycles of docetaxel or cabazitaxel, and less than ten, with two consecutive rising PSA values, checked at least 7 days apart
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 or > 6 weeks since last bicalutamide or nilutamide; the PSA value at the screening should be > 2 ug/L (2 ng/mL)
PSA blood test within 60 days prior to registration
Subjects with a rising PSA value > 2 ng/mL in at least 2 measurements, at least 1 week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for the rising PSA is required to document progression.
Evidence of rising PSA on ADT
PSA >= 0.1 after radical prostatectomy (value w/in 3 months of registration) AND at least 1 unfavorable risk factor listed below\r\n* Gleason 8-10\r\n* PSA > 0.5\r\n* Pathologically positive lymph nodes\r\n* pT3 or pT4\r\n* PSA doubling time (DT) < 10 months\r\n* Negative margins\r\n* Persistent PSA after radical prostatectomy (RP) (PSA never dropped below 0.1 after RP)\r\n* Local/regional recurrence on imaging\r\n* Decipher “high risk” (a Medicare-reimbursed test for risk of metastases after prostatectomy)
One of the following pathologic classifications\r\n* T3N0 disease with or without a positive surgical margin or\r\n* T2N0 disease with or without a positive surgical margin\r\n** Those with T2N0 disease and a negative margin must have a detectable prostate-specific antigen (PSA) following radical prostatectomy or\r\n** Must have had an undetectable PSA after prostatectomy and has since had a rise in post-operative PSA to 0.2 ng/mL or greater
Patients with rising PSA on two successive measurements at least 2 weeks apart
Most recent PSA value more than 18 months ago
A minimum of three PSA values, each at least 4 weeks apart, to calculate PSA-doubling time (DT); the last PSA level prior to enrollment must be at least 1.0 ng/mL and be rising over the prior value
PSA must be at least 1 ng/ml and rising on two successive measurements at least two weeks apart
Progressive, castration-resistant prostate cancer demonstrated during continuous antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mL
Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as most recent treatment must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washout
Documented prostate cancer progression as assessed by the investigator with one of the following: PSA progression defined by a minimum of 3 rising PSA levels with an interval of >=1 week between each determination. The PSA value at screening must be >=5 microgram (µg)/L (5 ng/mL) if PSA is the only indication of progression; subjects on systemic glucocorticoids for control of symptoms must have documented PSA progression by PCWG3 while on systemic glucocorticoids prior to commencing Cycle 1 Day 1 treatment.
PSA is mandatory (< 60 days prior to registration)
Patients must have rising PSA on two successive measurements, at least 2 weeks apart
Subjects must have castrate levels of testosterone (?50 ng/dl [1.7 nmol/L]) and have progressive disease at Screening defined as PSA rise determined by a minimum of 2 rising PSA values ?1 week between each assessment. The PSA value at the Screening visit must be ?2ng/mL with or without:
Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
PSA and the screening PSA assessed by the central laboratory (central PSA) should be ? 2 µg/L (2 ng/mL:
Increasing PSA level: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2. Inclusion criterion only for patients entering phase Ib expansion cohort:
Patients must be receiving continuous enzalutamide treatment and show a rise in PSA level: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2.
PSA blood test within 60 days prior to registration
Baseline serum PSA value performed with an Food and Drug Administration (FDA)-approved assay (e.g., Abbott, Hybritech) within 60 days prior to registration\r\n* Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT; (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride
PSA >= 0.5 but =< 50
Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 month
Patients must have PSA progression after local treatment:\r\n* PSA values for patients after surgery (or surgery and salvage/adjuvant radiation) must be greater than 0.2 ng/mL, determined by two measurements, at least 1 month apart and at least 6 months after prostatectomy OR\r\n* PSA values for patients after radiation must be greater than or equal to 2.0 ng/ml greater than the nadir achieved after radiation, determined by two measurements at 1 month apart and at least 6 months after the radiation treatment is completed; (patients who received adjuvant or salvage radiation after prostatectomy must have PSA of greater than or equal to 0.2)\r\n* The first two PSA values, along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value)\r\n* PSA doubling time using the mkscc.org PSA doubling time calculator must be greater than 4 months
Progressive disease on androgen deprivation therapy at screening defined as a minimum of two sequentially rising prostate-specific antigen (PSA) values (PSA1 < PSA2 < PSA3);
The serum PSA should be less than or equal to 15 ng/ml; study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of androgen deprivation therapy (ADT); (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride
Participants who received a first generation anti-androgen (eg, bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after the washout period
Rising serum PSA levels documented by 3 values over the last 6 months prior to study enrollment. Each value must be greater than 2 weeks from the previous value.
Progressive disease (PSA, radiologic, symptomatic) following abiraterone acetate and/or enzalutamide (prior chemotherapy and sipuleucel-T is allowed); PSA progression is defined as baseline increase followed by any PSA increase >= 1 week apart
COHORT B: Histologically confirmed prostate cancer with progressive disease, defined as:\r\n* Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 week apart); the 50% rise in PSA is across the 3 determinations, and these determinations do not need to be sequential\r\n* PSA doubling time of =< 12 months as calculated according to the Memorial Sloan-Kettering Cancer Center nomogram
Prostate-Specific Antigen (PSA) progression defined by a minimum of 2 rising PSA levels with an interval of at least 1 week between each draw;
Patients must have evidence of biochemical (PSA) relapse after prostatectomy, defined by one rise in PSA above a baseline detectable value (>= 0.05 ng/mL) using measurements taken at least 4 weeks apart from each other (all PSA values must be within 12 months of study entry)
Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises, at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL)
Patients who received a first generation anti-androgen (for example, bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization AND must show continuing disease (PSA) progression (an increase in PSA) after washout
Patient must have a histological diagnosis of adenocarcinoma of the prostate and 2 rising pre-study PSA values >= 1 ng/ml at least 1 week apart within 28 days prior to enrollment
Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 month
Evidence of disease progression on ADT. Patients must have two serial rises in PSA from nadir, with at least 1 week between PSA measurements, with a minimum PSA of 2 ng/mL, OR patients must have radiographic evidence of progression. Nadir is defined as the lowest PSA value after beginning the most recent therapy for metastatic CRPC.
Prostate cancer recurrence after definitive local therapy (radical prostatectomy and/or radiation therapy) as evidenced by rising serum PSA, without evidence of metastases by bone scan or CT scan. a) After radiation: A rising PSA taken to indicate recurrent prostate cancer in patients with previous definitive external beam radiotherapy will be defined as PSA of 1.0, b) After Radical Prostatectomy: A rising PSA taken to indicate recurrent prostate cancer in patients with previous radical prostatectomy will be defined by the criteria of the American Urological Association as any PSA measurement of 0.2, with a subsequent measurement >0.2 ng/mL
Histologically confirmed prostate cancer (per standards at institution of participant registration) currently with progressive disease, defined as:\r\n* Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 week apart); the 50% rise in PSA is across the 3 determinations, and these determinations do not need to be sequential; AND\r\n* Prostate-specific antigen doubling time (PSADT) =< 9 months as calculated according to the Memorial Sloan-Kettering Cancer Center nomogram
Androgen dependent disease measured by declining prostate-specific antigen (PSA) and do not display signs of progression demonstrated by a rising PSA
Patient must have biochemical evidence of prostate-specific antigen (PSA) including one of the following:\r\n* Biochemical recurrence (defined as nadir + 2 rises measured at least 2 weeks apart)\r\n* PSA doubling time of less than or equal to 6 months OR\r\n* Persistently elevated PSA (PSA post prostatectomy of 0.2 ng/mL if standard assay or greater than 0.05 if ultrasensitive PSA assay)
Patients must have high-risk clinical stage D0 disease defined by the following:\r\n* In patients previously treated by prostatectomy, must have evidence of rising prostate specific antigen (PSA) with measurements at least two weeks apart, and final serum PSA value must be >= 2 ng/mL\r\n* In patients previously treated with ablative radiation therapy, an absolute increase in serum PSA by at least 2 ng/mL over nadir PSA value after radiation therapy\r\n* All patients must have at least four serum PSA values determined over a 12-week-to-six-month period of time prior to study entry from the same clinical laboratory; all available PSA values during this period (up to 6 months) will be used to calculate a PSA doubling time, according to the Memorial Sloan-Kettering Cancer Center nomogram\r\n* The PSA doubling time calculated from this nomogram, up to and including the value obtained at screening, must be < 12 months
Evidence of CRPC indicated by history of progression despite standard hormonal therapy (by PSA and/or imaging studies)
Patients with histologically proven prostate cancer and tumors limited to the prostate (including seminal vesicle involvement, provided all visible disease was surgically removed) that have completed local therapy and have an elevated PSA after surgery or rising PSA after radiation therapy
All patients must have evidence of biochemical progression as determined by a reference PSA value followed by 1 confirmatory rising PSA value, higher than the previous value, obtained at least 2 weeks apart; all of these PSA values must be obtained at the same reference lab, and all must be done within 6 months prior to enrollment
Demonstrated PSA progression within 12 weeks of study participation
PSA progression according to PCWG2 criteria with 3 consecutive rising PSA measurements, all collected at least 1 week apart
Two consecutively rising PSA values or two out of three rising PSA values (2.0 ng/mL is the minimum ending value for PSA) at a minimum of 1-week intervals
Progressive disease based on any one of the following:\r\n* For patients with measurable disease, progression will be defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria\r\n* For patients with non-measurable disease, a positive bone scan and elevated PSA will be required; PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression for the purposes of eligibility\r\n* Radionuclide bone scan: new metastatic lesions\r\n* Patients whose sole manifestation of progression is an increase in disease-related symptoms are not eligible
c. Biochemical recurrence following local therapy, either surgery or radiation. Rising PSA defined as:
Previous inclusion in the study (e.g., a patient who has had negative TRUS and MRI-guided biopsies but continues to have a rising PSA)
Rising PSA defined (PCWG2).
Biochemically relapsed disease with a rising PSA on at least two successive measurements at least two weeks apart after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy (RT) with curative intent; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to documents progression
Castrate-resistant disease, as evidenced by either:\r\n* Rising PSA on 2 consecutive measurements at least 2 weeks apart with concurrent documented serum testosterone < 50 ng/dL at the time of PSA measurement, or\r\n* Rising PSA on 2 consecutive measurements at least 2 weeks apart measured within 3 months after last LHRH agonist/antagonist injection
T1a or b prostate carcinoma involving < 5% of resected tissue and PSA within normal limits (WNL) since resection
PSA progression defined by a minimum of two rising PSA levels with an interval of ? 1 week between each determination. The PSA value at the Screening visit should be ? 2 ng/mL
Patients will need to have documentation of metastatic disease in bone and/or soft tissue, and a baseline PSA of >= 5 ng/ml; patients with biochemical failures, with rising PSA (baseline PSA does not need to be >= 5 ng/ml to be eligible), without metastatic disease are also eligible if castration therapy is indicated for a minimum of 7 months and for these patients any PSA value is permitted
Biochemical recurrence following prostatectomy or radiation to the prostate, defined as at least 3 PSA rises, with each PSA determination at least 4 weeks apart, and each PSA value >= 0.2 ng/mL
Known progressive castration-resistant disease, defined as: \r\n* Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first treatment, each measurement at least one week apart; serum PSA at screening >= 2 ng/mL; or \r\n* Documented appearance of new lesions by bone scintigraphy
PSA < 25
Have a PSA < 25
Rising PSA (at least two consecutive rising PSAs) after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation for biochemical recurrence after radical prostatectomy\r\n** PSA greater than or equal to 0.2 ng/mL measured more than 6 weeks after RP\r\n* Post-radiation therapy–American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition of biochemical recurrence after radiation therapy\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSA
SUB-STUDY III: Two consecutive rising PSA values
Persistently elevated PSA
Elevated PSA level (>= 4) and a prior negative standard biopsy of the prostate
Rising PSA on two observations taken at least 1 week apart
PSA recurrence not verified by elevated PSA as discussed in the eligibility section
PSA levels to be taken within 2 weeks of antibody administration
Detectable PSA, defined as PSA detectable and rising on 2 or more subsequent determinations
Failure of PSA to nadir after surgery
biochemical progression (PSA)
PSA<50
PSA > 20
Baseline serum PSA value performed with an FDA-approved assay within 120 days prior to registration. Study entry PSA should not be obtained within 10-day period following prostate biopsy or following initiation of hormonal therapy
Curatively treated cervical intraepithelial neoplasia or prostate carcinoma with current prostate specific antigen < 0.01 ng/mL; or
Prostate specific antigen (PSA) < 20, within 6 months of study entry\r\n* Participants who are currently receiving dutasteride (or have received it within the last 90 days) or finasteride (or have received it within the last 30 days) must have a PSA of =< 10
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;
Prostate specific antigen (PSA) =< 80 ng/ml, obtained within 3 months
Most recent prostate specific antigen (PSA) within 60 days of enrollment
Prostate specific antigen (PSA) =< 10 ng/mL within 90 days prior to registration; PSA should not be obtained within 10 days after prostate biopsy
Prostate specific antigen (PSA) >= 0.2 ng/ml that is confirmed with a second PSA measurement
PSA values < 20 ng/ml within 90 days prior to registration, done either prior to prostate biopsy or at least 21 days after prostate biopsy
Prostate specific antigen (PSA) =< 20 ng/dL
Prostate specific antigen (PSA) of less than 10 ng/ml
No distant metastases on bone scan (only necessary if prostate specific antigen [PSA] >= 10 ng/ml and/or Gleason score >= 7)
Serum prostate specific antigen (PSA) level < 20 ng/ml
Prostate-specific antigen (PSA) < 10 ng/ml (this will be the PSA level prompting the initial prostate biopsy)
Known active invasive malignancy (except for non-melanomatous skin cancer or anaplastic thyroid cancer; the presence of prostate cancer confined to the prostate with a prostate-specific antigen [PSA] =< 1 ng/mL for more than 6 months also is allowed)
Prostate-specific antigen doubling time of ? 10 months and PSA > 2ng/ml.
Specific eligibility criteria for Part 2 CRPC expansion cohort: Prostate-Specific Antigen (PSA) levels >=2.0 ng/mL. Note: If PSA level has been obtained within 14 days of Screening, this test does not need to be repeated and the result previously obtained may be used for the Screening value.
Serum prostate-specific antigen (PSA) ? 15ng/mL.
Patients with a prostate serum antigen (PSA), equal to, or more than, 5 ng/mL.
Another primary malignancy that has not been in remission for at least 2 years; non-melanoma skin cancer, intraepithelial carcinoma of the cervix, or prostate cancer with a current prostate specific antigen (PSA) =< 0.1 ng/mL is allowed
Prostate-specific antigen (PSA) < 20 ng/dl
Serum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [?g/L]) OR
Prostate specific antigen (PSA) value can be undetectable up to a value of 2.0 within 30 days prior to study entry
Prostate specific antigen (PSA) > 1 ng/ml, unless anaplastic features are present
Serum prostate specific antigen (PSA) < 10 ng/mL            \r\n* NOTE: baseline PSA for determination of eligibility must be measured after discontinuation of any 5-alpha reductase inhibitors
serum prostate specific antigen (PSA) ?0.5 ng/mL and ?10 ng/mL;
Have abnormal digital rectal examination, or abnormal prostate specific antigen (> 4.0 ng/ml), or obstructing prostate, or biopsy proven prostate cancer
Had a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia or treated prostate cancer with a prostate-specific antigen (PSA) of <2.0 ng/mL;
Measurable disease on computed tomography (CT) or evaluable disease with an elevated prostate specific antigen (PSA)
Scheduled TRUS-guided biopsy because of clinically suspected prostate cancer (abnormal serum prostate-specific antigen [PSA] level and/or abnormal digital rectal examination)
Curatively treated cervical intraepithelial neoplasia or prostate carcinoma with current prostate specific antigen (PSA) < 0.01 ng/mL; or
Serum prostate specific antigen equal to or less than 10 ng/mL
Prostate-specific antigen (PSA) level of 0.1 - 50 ng/dl
Prostate-specific antigen (PSA) >= 0.2 ng/ml
Diagnostic prostate specific antigen (PSA) =< 10 ng/ml
Post-operative prostate-specific antigen (PSA) < 0.2 ng/mL by 120 days after prostatectomy
Detectable prostate-specific antigen (PSA)
Prostate-specific antigen (PSA) >= 0.1 ng/ml at time of enrollment.
With a suspicion (elevated prostate specific antigen [PSA] and/or abnormal digital rectal exam)/diagnosis of prostate cancer
Prostate specific antigen (PSA) measurement =< 42 days prior to study enrollment
Serum prostate specific antigen (PSA) =< 20 ng/ml within 3 months of study enrollment
Patients with known or suspected prostate disease based on clinical data will be included in the study; patients with intermediate to high grade prostate cancer (Gleason’s score >= 7 and prostate-specific antigen [PSA] of > 10ng/dl) will be referred from the outpatient clinics after evaluation by the treating physicians
Having elevated prostate specific antigen (PSA) (> 2.5 ng/ml) and no palpable nodule on digital rectal exam (DRE)
Prostate-specific antigen (PSA) within 4 months prior to study consent or within 30 days after study consent < 10 ng/mL
Patient has suspected recurrence based on biochemical data (prostate-specific antigen [PSA] > 2 ng/mL)
Prostate specific antigen (PSA) < 10 ng/mL
Patient has suspected recurrence based on biochemical data (prostate specific antigen [PSA] > 2 ng/mL)
For prostate cancer patients, prostate specific antigen (PSA) > 5
A rise in prostate-specific antigen (minimal value 2 ng/milliliter (mL); ?3 consecutive rising values)
Prostate-specific antigen (PSA) < 50 ng/mL
Baseline PSA nadir >= 0.2 ng/ml (post-operative value is never undetectable) obtained prior to step 1 registration
Previously untreated localized adenocarcinoma of the prostate with the following clinical findings:\r\n* Clinical stage by digital rectal exam of either T1c or T2a/b (limited to one side of the gland); (American Joint Committee on Cancer [AJCC], version 7) or cT1a-c or 2a or 2b, stage group IIA or IIB (AJCC, version 8); both versions 7 and 8 staging should be recorded\r\n* Patients in active surveillance who elect to be treated are eligible if they meet protocol requirements\r\n* Stages T1a-T1b are eligible if patient underwent transurethral prostatic resection (TURP) previously Gleason score must be Gleason 7(3+4) with a PSA < 20 ng/mL, or Gleason 6(3+3) with a PSA > 10 ng/mL and < 20 ng/mL; (AJCC, version 7) or group grade 1 or 2, stage Group IIA or IIB (AJCC version 8)\r\n** If patient is receiving a 5-alpha reductase inhibitor at the time of enrollment the baseline PSA value will be assumed to be double the initial value and the medication should be discontinued but does not need to have a washout period to participate, to remain eligible a PSA drawn while still on the medicine must be:\r\n*** < 10 ng/mL to remain eligible if Gleason 7(3+4) \r\n**** Stratification level 1 if PSA < 5 ng/mL and level 2 if less than 10 ng/mL\r\n*** > 5 ng/mL and less than 10 ng/mL for Gleason 6(3+3) \r\n**** Stratification level 3\r\n* Percent of submitted positive core biopsies must be < 50% of all sextants\r\n** NOTE: all cores from a targeted lesion will be counted as an N of 1 core for calculating percent positive cores in total\r\n* The prostate volume must be < 60 cc as reported at time of biopsy or by separate measure with ultrasound or other imaging modalities including magnetic resonance imaging (MRI) or computed tomography (CT) scan
Recurrent prostate cancer following primary therapy as defined by:\r\n* Post-radical prostatectomy: Any PSA >= 0.4 ng/ml\r\n* Post-primary radiotherapy: PSA >= 2 ng/ml above a post-radiotherapy nadir\r\n* Post-primary androgen-deprivation therapy: A confirmed rise of PSA >= 2 ng/ml above a post-therapy nadir
For patients with castrate levels of circulating androgen levels (testosterone < 50 ng/dl):\r\n* PSA levels must be >= 0.4 ng/ml (if history of radical prostatectomy) or >= 2 ng/ml (if history of non-surgical primary treatment) and found to be increasing on at least two occasions >= 1 week apart\r\n* At least 4 weeks must have elapsed since any changes to hormonal therapy, including at least 4 weeks since flutamide and at least 6 weeks since bicalutamide, nilutamide, or enzalutamide
PSA ? 2 ng/ml
Evidence of disease recurrence or progression as evidenced by a PSA > 0.20; this requires 2 consecutive rises in PSA, at least 1 week apart, over the post-prostatectomy nadir or one PSA value above 0.20 ng/mL if the patient failed to achieve a post-prostatectomy nadir of < 0.2 ng/mL
PSA > 4.0 ng/mL
Baseline (pre-treatment) serum troponin T (TnT) >= 0.03 ng/mL; Troponin T levels may be rechecked and therapy given if levels decrease to < 0.03 ng/mL
PSA values < 10 ng/ml within 90 days prior to randomization. Either done prior to biopsy or at least 21 days after prostate biopsy.
Absolute PSA > 20 ng/mL AND/OR
Very fast PSA doubling time of less than 4 weeks, if the absolute PSA is > 2 ng/mL or an absolute PSA value of greater than or equal to 20 ng/ml
Screening PSA > 0.5 ng/mL
Screening PSA must be >= 1.0 ng/mL
PSA < 15 ng/ml or PSA density < 0.15 ng/ml2 in patients with a PSA > 15 ng/ml
PSA must be < 30 ng/mL at study entry
Serum PSA >= 2.0 ng/mL
For patients following radical prostatectomy: 2 absolute PSA values > 0.2 ng/ml
PSA >= 2 ng/mL
Serum PSA =< 10.0 ng/ml
PSA values < = 20 ng/ml within 90 days prior to randomization. Obtained prior to biopsy or at least 21 days after prostate biopsy.
PSA values < 2 ng/ml within 90 days prior to enrollment. Obtained at least 6 weeks after surgery
Has a serum vitamin D level of ? 50 ng/mL
Biochemical progression defined as follows:\r\n* For patients following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]- American Society for Radiation Oncology [ASTRO] consensus criteria)\r\n* For patients following radical prostatectomy: rising PSA after surgical procedure (patients must have a PSA >= 0.8 ng/mL)
PSA =< 30 ng/mL
Serum PSA ?10 ng/mL.
Evidence of disease recurrence or progression as evidenced by a PSA > 0.20 ng/ml; this requires 2 consecutive rises in PSA, at least 1 week apart, over the post-prostatectomy nadir or one PSA value above 0.20 ng/mL if the patient failed to achieve a post-prostatectomy nadir of < 0.2 ng/mL
PSA ? 4.0 ng/mL
PSA >= 4 ng/ml
PSA >= 20 ng/dL
Has a serum PSA concentration at the Screening visit of > 2.0 ng/mL (2.0 ?g/L), or, when applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 ?g/L) or post radiotherapy, cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 ?g/L) above the post interventional nadir;
Creatinine =< 1.4 ng/mL for females; =< 1.5 ng/mL for males; patients with creatinine =< 2.0 ng/mL may still be eligible if in the opinion of the investigator, the benefits of treatment outweigh the risks
Absolute PSA >=1 ng/ml; prior undetectable PSA post-prostatectomy is not required
PSA > 2 ng/mL at baseline or prior to initiation of hormonal therapy
Screening PSA must be >= 1.0 ng/mL
Baseline serum ferritin level >= 300 ng/mL
Serum ferritin < 50 ng/mL
Baseline serum vitamin D total 25-hydroxy level below 66 ng/ml
Patients with vitamin D total 25-hydroxy level above 66 ng/ml at baseline testing
Patient has a PSA of greater than 80 ng/ml obtained no greater than 3 months prior to randomization
Serum PSA <20 ng/ml
PSA > 10 ng/mL in screening
Maximum PSA =< 20 ng/ml (not within 20 days after biopsy)
PSA > 100 ng/mL
PSA < 150 ng/mL
PSA >= 150 ng/mL
For patients with metastatic prostate cancer, PSA >= 2 ng/mL, except for patients who have recently started androgen deprivation therapy with PSA < 2 ng/mL
Serum PSA > 160 ng/dL
Baseline vitamin D level greater than 50 ng/mL
PSA >= 2.0 ng/mL
Very low risk category (T1c, GS ?6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores positive, ?50% cancer in any core, PSA density <0.15 ng/mL/g)
PSA of greater than 10ng/ml
PSA > 10 ng/ml
CEA plasma levels > 5 ng/mL.
Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
CEA plasma levels > 5 ng/mL
Prostate cancer with a current PSA level < 0.1 ng/mL.
Must have a vitamin D level >= 30 ng/mL after repletion
Serum ferritin < 50 ng/mL.
Normal serum CEA levels (< 3 ng/ml) at the time of registration
Serum PSA level > 20 ng/ml
Serum PSA >= 2.0 ng/ml at study enrollment
Patients must have a PSA >= 2 ng/mL obtained within 90 days prior to registration
Serum PSA <10 ng/mL undergoing active surveillance may be enrolled with agreement of the sponsor.
Screening PSA by the central laboratory ? 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;
PSA ? 15 ng/ml
PSA > 20 ng/ml
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.
PSA progression defined as 25% increase over a baseline value of > 2 ng/ml 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. Baseline is defined as the PSA nadir level since commencing most recent prior therapy
A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7
pT2 with a negative surgical margin and PSA < 0.1 ng/mL
PSA ? 20 ng/mL;
PSA > 20 ng/mL
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.
Prostate cancer with a current PSA level < 0.1 ng/mL.
Patient with PSA less than or equal to 10 ng/mL
PSA < 10 ng/mL =< 30 days prior to registration
Biochemical progression after definitive radiation or surgery defined as follows:\r\n* For patients following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] consensus criteria)\r\n* For patients following radical prostatectomy: rising PSA after surgical procedure; (patients must have a PSA >= 0.8 ng/ml)
PSA =< 30 ng/mL
Patients with prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy), but with undetectable PSA (<0.2 ng/mL).
The screening PSA (PSA3) must be ? 2 ?g/L (? 2 ng/mL).
Patients must have a minimum serum PSA level of >2 ng/ml that is rising based on the Prostate Cancer Working Group 2 criteria.
PSA value within 4 weeks of starting therapy less than 20 ng/mL for hormone-naïve patients (defined as hormone-naïve patients and patients who received hormone therapy in the past who currently have total testosterone greater than 50 ng/dL) or less than 60 ng/mL for hormone-independent patients.
An elevated PSA level of > 2 ng/mL for patients progressing by PSA criteria is required (last confirmatory sample must be > 2 ng/mL)
Serum PSA ?2 ng/mL (?g/L)
Patients must have an absolute PSA level between > 0.05 and < 0.7 ng/mL at the time of study entry
PSA >= 2.0 ng/mL
Biochemical progression defined as follows:\r\n* For patients following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] consensus criteria)\r\n* For patients following radical prostatectomy: rising PSA after surgical procedure (patients must have a PSA >= 2 ng/ml)
PSA =< 20 ng/mL
Patients must have a PSA >= 2 ng/mL at the time of diagnosis of prostate cancer or later
PSA > 2 ng/mL
PSA > 2 ng/mL (at the time of enrollment or prior to initiation of docetaxel)
Evidence of measurable disease either by RECIST 1.1 or elevation of serum tumor markers (AFP > 15 ng/mL or HCG > 2.2 mIU/ml)
The most recent of the PSA values must be >= 2.0 ng/ml; this measurement must be obtained within 1 month prior to enrollment
Pre-registration serum PSA level =< 100 ng/mL
All patients must have a PSA >= 2 ng/mL
300 ng/mL < serum ferritin < 1,500 ng/mL (Values within 10% difference above 1500 ng/ml or 10% difference below 300 ng/ml may be accepted at the investigator's discretion.
Prostate cancer with a current PSA level < 0.1 ng/mL.
After radical prostatectomy, two PSA measurements of ? 1.0 ng/mL at least one week apart;
After cryosurgery, two PSA measurements of ? 2.0 ng/mL at least one week apart;
A PSA value of at least 2 ng/mL is required at study entry.
Biochemical disease progression after radical prostatectomy and/or radiation therapy (external-beam radiation therapy and/or brachytherapy), and no radiographic evidence of metastases\r\n* Men with history of radical prostatectomy are required to have baseline PSA > 0.5 ng/mL (prior treatment with neoadjuvant, adjuvant, or salvage radiation therapy is allowed, again, with screening PSA greater than or equal to 0.5 ng/mL required for eligibility)\r\n* Men treated with primary radiation therapy are required to have baseline PSA >= 1.0 ng/mL above their post radiation nadir for men who were treated with primary radiation therapy (external beam and/or brachytherapy); men who had primary radiation therapy followed by salvage prostatectomy are eligible if screening PSA is greater than or equal to 0.5 ng/mL\r\n* Men with previous neoadjuvant adjuvant hormone therapy are eligible if testosterone level at screening is non-castrate (>= 50 ng/dl); men previously treated with intermittent hormonal therapy are also eligible if level of testosterone at screening is non-castrate (>= 50 ng/dl)
PSA at least 2 ng/mL
Minimum PSA:\r\n* If no prior androgen deprivation therapy (ADT) for biochemical relapse:\r\n** 1.0 ng/mL if prior radical prostatectomy with or without adjuvant/salvage radiation therapy, confirmed by repeat measurement at least 2 weeks later, or\r\n** Nadir + 2 ng/mL if prior RT alone without prior radical prostatectomy, confirmed by repeat measurement at least 2 weeks later\r\n* If prior ADT for biochemical relapse:\r\n** 4.0 ng/mL or > 2 ng/mL above nadir on prior cycle of ADT, whichever is higher, confirmed by repeat measurement at least 2 weeks later
Have a PSA less than 10 ng/mL,
Have a PSA density less than 0.15 ng/ml/cc,
Have a PSA velocity less than 2 ng/ml yearly in the year prior to diagnosis,
PSA must be < 50 ng/mL at study entry
Screening PSA >= 0.5 ng/mL for men who had a prostatectomy; prior treatment with neoadjuvant, adjuvant or salvage radiation therapy is allowed, again, with screening PSA >= 0.5 ng/mL required for eligibility
Screening PSA >= 1.0 ng/mL above their postradiation nadir for men who were treated with primary radiation therapy (external beam and/or brachytherapy); men who had primary radiation therapy followed by salvage prostatectomy are eligible if screening PSA >= 0.5 ng/mL
Stable and undetectable PSA level (PSA < 0.1 ng/mL using an assay that has a functional sensitivity of 0.1 ng/mL) for at least two years after radical prostatectomy
PSA > 50 ng/dl
PSA < 0.5 ng/dL
Serum vitamin D 25, hydroxy (OH) < 12 ng/mL
Detectable PSA, defined as PSA >= 0.01 ng/ml
Persistent PSA after prostatectomy for PSA >= 0.2 ng/mL
Vitamin D insufficiency, defined as 25(OH)D =< 32 ng/ml
Ferritin >= 800 ng/mL
Serum vitamin D level >= 10 ng/ml
PSA of 2-10 ng/mL
25(OH)D3 level less than 20 ng/ml prior to stage 2 initiation
Screening serum PSA < 20 ng/mL; for men treated with 5-alpha-reductase inhibitors (e.g., finasteride, dutasteride), PSA needs to be < 10 ng/mL
PSA within the past 2 months is between 3 and 20 ng/ml if patient received local radiation OR between 0.4 and 20 ng/ml if patient received prior radical prostatectomy
Patient with PSA less than or equal to 20 ng/mL
25-hydroxy vitamin D3 (25[OH]D3) level less than 20 ng/mL prior to study initiation
COHORT I: Biochemical recurrence defined as any of the following:\r\n* PSA >= 0.2 ng/mL in at least two consecutive tests within 6 months of date of consent for patients treated with surgery, radiation therapy, brachytherapy, or cryotherapy\r\n* PSA >= 0.2 ng/ml above the most recent therapy nadir for patients who have received additional treatment in the recurrent setting
Proven biochemical recurrence as defined by American Urological Association (AUA) recommendation: PSA greater than or equal to 0.2 ng/mL measured more than 6 weeks after radical prostatectomy
PSA values ranging from 0.2 ng/mL to 2 ng/mL
Rising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured more than 6 weeks after RP and,\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy –American Society for Therapeutic Radiology and Oncology (ASTRO) (ASTRO)-Phoenix consensus definition\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSA
Rising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* If post-radical prostatectomy, PSA > 0.2 ng/mL measured > 6 weeks post-operatively and confirmatory persistent PSA greater than 0.2 ng/mL (American Urological Association [AUA] recommendation for biochemical recurrence)\r\n* If post-radiation therapy, PSA that is equal to, or greater than, a 2 mg/mL rise above PSA nadir (American Society for Radiation Oncology [ASTRO] recommendation for biochemical recurrence)
SUB-STUDY II: Biochemical recurrence with PSA > 0.2 ng/mL on two successive tests
Rising PSA after definitive therapy with prostatectomy or radiation therapy.\r\n* Post radical prostatectomy (RP)\r\n** PSA equals to or greater than 0.2 ng/mL measured more than 6 weeks after RP\r\n* Post-radiation therapy – American Society for Therapeutic Radiation and Oncology (ASTRO)-Phoenix consensus definition\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSA
PSA < 0.1 ng/ml at enrollment
PSA >= 15 ng/mL
Rising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured 6–13 weeks after RP\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy – American Society for Therapeutic Radiology and Oncology (ASTRO)-Phoenix consensus definition \r\n** Nadir plus (+) greater than or equal to 2 ng/mL rise in PSA
PSA < 25 ng/mL
Rising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urology Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured 6–13 weeks after RP\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy –American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition\r\n** Nadir + greater than or equal to 2 ng/mL rise in PSA
Serum PSA level >= 0.2 ng/mL at least 45 days prior to study enrollment
Two PSA values >= 0.2 ng/mL at least 4 weeks after prostatectomy
Patient will have suspicion of recurrent prostate carcinoma as defined by: the American Society for Therapeutic Radiology and Oncology (ASTRO)-Radiation Therapy Oncology Group (RTOG) Phoenix criteria of elevated prostate-specific antigen (PSA) greater than nadir plus 2 ng/ml with absolute PSA >= 4.0 ng/ml with any doubling time (DT) or with PSA 2.0-3.99 ng/ml with DT =<10 months
Rising PSA after definitive therapy with prostatectomy or radiation therapy (external beam or brachytherapy)\r\n* Post radical prostatectomy (RP) – American Urological Association (AUA) recommendation\r\n** PSA greater than 0.2 ng/mL measured more than 6 weeks after RP and\r\n** Confirmatory persistent PSA greater than 0.2 ng/mL\r\n* Post-radiation therapy –American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition\r\n* Nadir + greater than or equal to 2 ng/mL rise in PSA
PSA < 10 ng/ml (this will be the PSA level prompting the initial prostate biopsy)
Abnormal prostate-specific antigen (PSA) blood test\r\n* > 2.5 ng/mL for men < 50 years (yrs) of age\r\n* > 3.5 ng/mL for men < 60 yrs of age\r\n* > 4.5 ng/mL for men < 70 yrs of age
ARM II ONLY: For patients status post prostatectomy, a PSA >= 0.2 ng/ml
Serum PSA ? 20ng/ml within the previous 3 months
Post prostatectomy: Detectable or rising PSA level that is >0.2 ng/mL with a second confirmatory level of >0.2 ng/mL
Post non-prostatectomy: PSA rise ? 2ng/mL over nadir
Increased PSA level >4 ng/mL
Abnormal serum PSA (total > 2.5 ng/ml or other clinically important biomarker parameters, including PSA velocity and density) associated with or without normal digital rectal examination
The presence of liver lesion(s) (as defined in a.) with AFP ? 400 ng/mL.
Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate- to high-risk for recurrence as determined by one of the following combinations:             \r\n* Gleason score 7-10 + T1c-T2b (palpation) + prostate-specific antigen (PSA) < 50 ng/mL (includes intermediate- and high-risk patients)\r\n* Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/mL OR Gleason score 6 + >= 50% (positive) biopsies + PSA < 50 ng/ml\r\n* Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL\r\n* Patients previously diagnosed with low risk prostate cancer undergoing active surveillance who are re-biopsied and found to have unfavorable intermediate risk disease or favorable high risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure
Clinical stage T1-2 N0 M0, Gleason score =< 7, PSA 20-100 ng/mL, or clinical stage any T N0 M0, Gleason score 8 -10, PSA =< 100 ng/mL, or clinical stage T3-4 N0 M0, any Gleason score, PSA =< 100 ng/mL, or clinical stage T1-2 N0 M0, Gleason score 4 + 3, PSA 10-20 ng/mL
Subject has high-risk features (e.g., based on Gleason score, PSA, clinical stage, % positive biopsies), and the treating physician feels the subject should undergo radical prostatectomy sooner than planned within the protocol
Histologically confirmed prostate adenocarcinoma (within 365 days of randomization) at intermediate risk for reoccurrence determined by at least one of the following: Gleason Score 7, PSA > = 10 and < = 20, T stage T2b - T2c
Must be considered either low-risk (T1-T2a, Gleason =< 6, prostate specific antigen [PSA] < 10 ng/mL) or favorable intermediate-risk (Gleason 3 + 4 = 7, percentage of positive biopsy cores < 50%, no more than one National Comprehensive Cancer Network [NCCN] intermediate risk factor)
A minimum of 10 core biopsies must be obtained at baseline. A prostate biopsy within 6 months from screening is allowed for entry requirements. Patients must meet intermediate risk criteria from Gleason score, T stage, and prostate specific antigen (PSA) value by National Comprehensive Cancer Network (NCCN) criteria: cT2b-T2c or Gleason 7 (3+4 or 4+3) or PSA 10-20 ng/mL. In addition, the Gleason 3+4 or 4+3 must be present
High risk prostate cancer defined as extracapsular extension (cT3a) or seminal vesicle involvement (cT3b) or invasion of adjacent structures (cT4), serum PSA > 20 ng/mL or Gleason score of 8 to 10 and/or regional lymph node or
Subjects must have the diagnosis of prostate cancer and be on active surveillance (AS). For the purpose of this study, active surveillance implies prostate-specific antigen (PSA) < 10 ng/mL, biopsy Gleason sum =< 6 with no pattern 4 or 5, cancer involvement of < 33% of biopsy cores, and clinical stage T1/T2a tumor.
The following tumor stage and Gleason scores: a) clinical >= stage T1c/T2 tumor with Gleason score >=8 b) clinical stage >= T2b tumor with Gleason score >= 7 and PSA > 10 ng/ml.
Histologically proven adenocarcinoma of the prostate and: Gleason > 8 OR prostatic specific antigen (PSA) > 20 and more than 1 positive core
High risk prostate cancer (per National Comprehensive Cancer Network [NCCN] criteria): Gleason score 8-10 or T3a or PSA > 20 ng/mL or very-high risk prostate cancer (per NCCN criteria): T3b-T4
Poor prognosis disease as defined by any of the following:\r\n* PSA nadir >=4.0, or\r\n* Gleason score 8-10, or\r\n* Time from ADT initiation to CRPC of =< 16 months
Favorable risk prostate cancer as defined by:\r\n* Very low-risk:\r\n** Clinical stage T1c disease\r\n** PSA density (PSAD) < 0.15 ng/mL\r\n** Gleason score 6\r\n** =< 2 core biopsies with =< 50% involvement of any biopsy core with cancer, or unilateral disease =< 2 core biopsies with any percentage involvement OR\r\n* Low risk:\r\n** Clinical stage =< T2a\r\n** PSA < 10 ng/mL\r\n** Gleason score 6 OR\r\n* Low-intermediate risk:\r\n** Clinical stage T1c\r\n** PSA < 10 ng/ml\r\n** Gleason 3+4 present in =< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy\r\n** Gleason 6 disease in all other cores (maximum of 2 cores with =< 50% involvement of any core, or if unilateral disease, any percentage involvement)
Men with a diagnosis of very low risk (< 5% risk of disease relapse after primary treatment, criteria; cT1c, Gleason =< 6, prostate-specific antigen (PSA) < 10 ng/mL, fewer than 3 positive biopsy cores =< 50% cancer in any core, PSA density < 0.15 ng/mL/g); low risk (10% risk of disease relapse after primary treatment, criteria; cT1-2a, Gleason =< 6, PSA < 10 ng/mL) prostate cancer
Patients belonging in the National Comprehensive Cancer Network (NCCN) high recurrence risk group:\r\n* High risk:\r\n** Clinical stage T3a, or Gleason score = 8-10, or PSA > 20 ng/mL
Pathological diagnosis of adenocarcinoma of the prostate, judged to be at high risk for recurrence based on any of the following (in accordance with the International Society of Urological Pathology (ISUP) Consensus 2005: Gleason score 8-10 OR Gleason score of 4+3 AND clinical T2b-4 AND PSA >20ng/mL OR N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or biopsy proven
Patients must have at least one of the following criteria:\r\n* The serum PSA should be greater than or equal to 20 ng/ml OR study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of antiandrogen therapy (ADT)\r\n* The Gleason score should be greater than or equal to 8 OR\r\n* Eligible patients must have appropriate staging studies identifying them as American Joint Committee on Cancer (AJCC) stage T3+ adenocarcinoma of the prostate gland; (MR stage T3a without other high risk factors permitted at investigator discretion)
Risk-group classification into the D’Amico or National Comprehensive Cancer Network (NCCN) ‘high-risk’ group, as defined by the presence of any one of the following high-risk factors:\r\n* Pre-biopsy prostate-specific antigen (PSA) >= 20\r\n* Biopsy Gleason score 8-10\r\n* Clinical stage T3
pT1-pT3pNxMx patients in whom standard National Comprehensive Cancer Network (NCCN) or American Urology Association (AUA) guidelines would suggest are at low risk for pelvic lymph node or metastatic disease and who would not require confirmatory imaging for metastatic disease; this includes patients with Gleason 6 or 7 (T2 disease) and prostate-specific antigen (PSA) less than 20
Patients must be candidates for long-term androgen deprivation in combination with EBRT for the treatment of high-risk or locally-advanced prostate cancer by the following criteria:\r\n* High risk disease: T3a or Gleason 8-10 or serum PSA > 20 ng/mL\r\n* Gleason 7 also allowed if > 50% of cores positive for cancer or PSA velocity > 2 ng/mL/year in preceding 12 months\r\n* Locally advanced (very high risk) disease: T3b-T4
Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate to high risk for recurrence as determined by one of the following combinations:\r\n* Gleason score 7-10 + T1c-T2b (palpation) + prostate specific antigen (PSA) < 75 ng/ml (includes intermediate and high risk patients)\r\n* Gleason score 6 + T2c-T4 (palpation) or > 50% (positive) biopsies + PSA < 75 ng/ml\r\n* Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/ml
National Comprehensive Cancer Network (NCCN) risk category very low, low, or intermediate risk:\r\n* Combined Gleason score =< 7\r\n* Prostate specific antigen (PSA) within three months of enrollment < 20 ng/ml\r\n* Clinical stage T1a-cN0M0 or clinical stage T2aN0M0
Prostate cancer categorized (as determined by central pathology review) as low risk is defined as T1c-T2a, PSA<10, N0, M0 (or presumed N0, M0 if CT/bone scan not done due to low risk of metastases), GS ? 6, ECOG status ?2 and estimated life expectancy >5 years OR intermediate risk is defined as T2b-T2c, PSA<20, N0, M0 (or presumed N0, M0 if CT/bone scan not done), GS ?7 (3+4 pattern only), ECOG status ? 2 and estimated life expectancy > 5 years. Prostate cancer categorized (as determined by central pathology review) to the very low risk category (T1c, GS ?6, PSA <10 ng/mL, fewer than 3 prostate biopsy cores positive, ?50% cancer in any core, PSA density <0.15 ng/mL/g) is not included.
Intermediate or high risk for recurrence according to the following criteria:\r\n* Two or more of the following intermediate risk features for recurrence\r\n** Gleason score = 7\r\n** Prostate-specific antigen (PSA) 10-20 ng/ml\r\n** Clinical stage T2b-T2c\r\n** Percent positive biopsy cores >= 50% OR\r\n* One or more of the following high risk features for recurrence\r\n** Gleason score 8-10\r\n** PSA > 20 ng/ml\r\n** Clinical stage T3a-T4
Eligible patients will have clinical stage T1c, T2a, or T2b, a pre-biopsy PSA level < 15 ng/mL and a biopsy Gleason score of 3+3 (or 3+4 if fewer than 50% of the total number of biopsy cores are involved by grade 3+4)
Patients belonging in one of the following risk groups:\r\n* Low: clinical stage (CS( T1b-T2a and Gleason 2-6 and PSA =< 10, or\r\n* Intermediate: CS T2b and Gleason 2-6 and PSA =< 10, or CS T1b-T2b, and Gleason 2-6 and PSA =< 20 ng/dL, or Gleason 7 and PSA =< 10 ng/dL
Inclusion Criteria include:\n\n          -  Histologically confirmed adenocarcinoma of the prostate\n\n          -  Patients choosing active surveillance\n\n          -  Patients meeting definition of NCCN low risk, intermediate risk OR patients having\n             only one NCCN high-risk feature\n\n               -  NCCN Low Risk is defined as having all of the following: PSA < 10 ng/ml, Gleason\n                  ? 6, T1-T2a\n\n               -  NCCN Intermediate Risk is defined as having at least one of the following and no\n                  high risk features: PSA 10-20 ng/ml, Gleason score =7, T2b-T2c\n\n               -  High Risk with a single high risk feature is defined as having only one of the\n                  following: PSA>20 ng/ml, Gleason score 8-10, or T3a\n\n               -  Excluded are those in the following risk groups: High risk with more than 1 high\n                  risk factor; Locally advanced/very high risk=T3b-T4; Metastatic: N1 or M1\n\n          -  Patients must be planning and medically able to tolerate multiple transrectal\n             ultrasound guided injections.\n\n          -  ECOG Performance status 0-2\n\n        Exclusion Criteria include:\n\n          -  Active liver disease, including known cirrhosis or active hepatitis\n\n          -  Patients on systemic corticosteroids (>10 mg prednisone per day) or other\n             immunosuppressive drugs\n\n          -  Known HIV+ patients\n\n          -  Regional lymph node involvement or distant metastases\n\n          -  Other current malignancy (except squamous or basal cell skin cancers)\n\n          -  Other serious co-morbid illness or compromised organ function that, in the opinion of\n             the investigator, would interfere with treatment or follow up\n\n          -  Prior treatment for prostate cancer except TURP. If prior TURP, patients must be\n             deemed able to receive prostate biopsy and multiple intra-prostatic injections by the\n             investigator\n\n          -  Patients taking 5-alpha-reductase inhibitors (e.g. finasteride, dutasteride)\n\n          -  Patients who had or plan to use ADT or have history of an orchiectomy.\n\n          -  Patients who are planning to undergo radical treatment for prostate cancer within 12\n             months.\n\n          -  Known sensitivity or allergic reactions to acyclovir or valacyclovir
Inclusion Criteria: All of the following criteria are mandatory for inclusion:\n\n          -  Histological confirmation of prostate adenocarcinoma with a minimum of 10 biopsy cores\n             taken within 18 months of randomisation.\n\n          -  Gleason score ? 3+4\n\n          -  Men aged ?18\n\n          -  Clinical and MRI stage T1c -T2c, N0-X, M0-X (TNM 6th Edition [72], See Appendix 1)\n\n          -  PSA ? 20 ng/ml\n\n          -  Pre-enrollment PSA must be completed within 60 days of randomisation\n\n          -  Patients belonging in one of the following risk groups according to the National\n             Comprehensive Cancer Network (www.nccn.org):\n\n               -  Low risk: Clinical stage T1-T2a and Gleason ? 6 and PSA < 10 ng/ml, or\n\n               -  Intermediate risk includes any one of the following:\n\n               -  Clinical stage T2b orT2c\n\n               -  PSA 10-20 ng/ml or\n\n               -  Gleason 3+4\n\n          -  WHO performance status 0 - 2\n\n          -  Prostate volume ? 90 cc measured within 6 months of randomisation (height*width*length\n             *?/6)\n\n          -  Ability of the research subject to understand and the willingness to sign a written\n             informed consent document\n\n        Exclusion criteria: One of the following criteria is sufficient for exclusion:\n\n          -  Clinical stage T3 or greater\n\n          -  Gleason score ? 4 + 3\n\n          -  High risk disease defined by National Comprehensive Cancer Network (www.nccn.org)\n\n          -  Previous malignancy within the last 2 years (except basal cell carcinoma or squamous\n             cell carcinoma of the skin), or if previous malignancy is expected to significantly\n             compromise 5 year survival\n\n          -  Prior pelvic radiotherapy\n\n          -  Prior androgen deprivation therapy (including LHRH agonists and antagonists and\n             anti-androgens)\n\n          -  Any prior active treatment for prostate cancer. Patients previously on active\n             surveillance are eligible if they continue to meet all other eligibility criteria.\n\n          -  Life expectancy <5 years\n\n          -  Bilateral hip prostheses or any other implants/hardware that would introduce\n             substantial CT artifacts\n\n          -  Medical conditions likely to make radiotherapy inadvisable eg inflammatory bowel\n             disease, significant urinary symptoms\n\n          -  Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery\n             unsafe in the opinion of the clinician (see section 11, Treatment).\n\n          -  Participation in another concurrent treatment protocol for prostate cancer
Presence of adverse pathologic features at the time of prostatectomy (positive surgical margin, pathologic\r\nT?stage 3?4 disease, pathologic Gleason score 8?10 disease, presence of tertiary Gleason grade 5 disease) OR documentation of rising prostate?specific antigen on at least two consecutive draws, with the magnitude of\r\nprostate?specific antigen exceeding 0.03 ng/mL
Have progressive advanced prostate cancer based on at least one of the following criteria:\r\n* Gleason score of ? 7\r\n* Any PSA\r\n* TNM clinical stage T3-T4, N1
At least one of the following:\r\n* Two or more high risk features OR\r\n** Gleason score 8-10\r\n** PSA >= 20 ng/mL within two months prior to registration\r\n** Clinical stage >= T3 disease, as determined by standard digital rectal examination (DRE)\r\n** Radiographic stage >= T3 disease as determined by a >= 75% probability of extracapsular extension or seminal vesicle invasion per reading radiologist\r\n* Any Gleason 9 or 10 disease OR\r\n* > 4 cores of Gleason 8 disease
Subjects must have one of the following risk factors:\r\n* Prostate-specific antigen (PSA) >= 20 and/or\r\n* Gleason score >= 8 and/or\r\n* Clinical or radiographic stage >= T3a per American Joint Committee on Cancer (AJCC) 7th Edition Staging Manual and/or\r\n* Radiographic pelvic lymph node positive disease and/or\r\n* At least two out of four of the following: PSA 10-19.9, Gleason score (GS) = 3+4, clinical stage = T2b/T2c, >= 50% positive biopsy cores
Intermediate risk or high risk prostate cancer patients who are candidates for radiation therapy:\r\n* Gleason >= 7 or\r\n* Clinical or pathological > T2b disease or\r\n* Prostate-specific antigen (PSA) >= 10 ng/mL
Patients must have low- or intermediate-risk adenocarcinoma of the prostate as defined by:\r\n* Low-risk disease\r\n** Histopathology score (Gleason sum): =< 6, and T-stage (per current American Joint Committee on Cancer [AJCC] staging criteria): T1c-T2a, and prostate-specific antigen (PSA) < 10\r\n* Intermediate-risk disease as either:\r\n** Histopathology score (Gleason sum): =< 6, T-stage (per current AJCC staging criteria): T1c-T2a, and PSA: > 10 but =< 20 Or\r\n** Histopathology score (Gleason sum): 7 with =< 50% cores positive, T-stage (per current AJCC staging criteria): T1c-T2a, and PSA < 10
Status post radical prostatectomy with sampling of the pelvic lymph nodes with histologically confirmed adenocarcinoma of the prostate, with the patients falling into either the “adjuvant high risk group” or the “salvage high risk group” as indicated below; in those cases where patients undergo a prostatectomy without any sampling of the pelvic lymph nodes, patients will be also considered eligible if they are found to have a negative pelvic computed tomography (CT) or magnetic resonance imaging (MRI) scan which shows no evidence of lymphatic nodal metastases after the prostatectomy\r\n* “Adjuvant High Risk Group” (undetectable, persistent or decreasing PSA levels before starting therapy) who have NO evidence of metastatic disease (i.e. no clinical symptoms or radiologic evidence) who MUST be able to start RT treatments within 6 months of radical prostatectomy with at least one of the 3 disease features:\r\n** Pathologic T2N0 disease and Gleason score >= 8, or\r\n** Pathologic T3aN0 disease with extracapsular extension and Gleason score >= 8, or\r\n** Pathologic T3bN0 disease with any Gleason score\r\n* “Salvage High Risk Group” are those patients with PSA biochemical failure defined by at least 1 detectable PSA level >= 0.2 ng/ml or at least 2 consecutive increases over baseline PSA levels at least one month apart, who have NO other evidence of metastatic disease (i.e. no clinical symptoms or radiologic evidence), and WITH AT LEAST ONE of the high risk disease features as defined below:\r\n** Pathologic T3bN0 disease with any Gleason score, or\r\n** Pathologic T2-3aN0 disease with Gleason score >= 8, or\r\n** Pathologic T2-3aN0 disease with PSA doubling time =< 10 months, or\r\n** Pathologic T2-3aN0 disease with pre-radiation therapy PSA level >= 1.0 ng/ml
Patients with prostate cancer on active surveillance at low risk for progression, defined as Prostate-Specific Antigen (PSA) < 10 ng/dL, Gleason score 6 and clinical stage tumor-1 (cT1) are permitted to be in the study at the discretion of the investigator (see exclusion criterion 10).
A history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score ?6; Prostate-specific Antigen (PSA) level undetectable.
Patient must fit D’Amico intermediate-risk criteria by clinical stage (T2b-T2c), prostate-specific antigen (PSA) (10-20 ng/mL), and/or Gleason score (Gleason 7)
Adenocarcinoma of the prostate proven by biopsy within 180 days of study registration with one of the following high risk criteria:\r\n* Gleason score 7 with PSA =< 20 ng/ml and clinical T1-2, or\r\n* Gleason score 8-10, PSA =< 20 ng/ml and clinical T1-2, or\r\n* PSA 10.1-40 ng/ml with Gleason score (GS) < 7 and clinical T1-2, or\r\n* Clinical T3 with Gleason score < 7 and PSA =< 10 ng/ml
Prostate adenocarcinoma without distant metastatic disease with either Gleason score >= 7, PSA >= 10 ng/ml, or T2b or greater disease
Adenocarcinoma of the prostate with intermediate risk disease T2b-T2c or Gleason score 7 or prostate specific antigen (PSA) 10-20 ng/ml, without metastatic disease
Pathologically (histologically) proven diagnosis of prostatic adenocarcinoma, at intermediate risk for recurrence, within 180 days prior to registration as determined by having one or more of the following intermediate-risk features: \r\n* Gleason score 7\r\n* Prostate specific antigen (PSA) > 10 but =< 20\r\n* Clinical stage T2b-T2c\r\n* Patients previously diagnosed with low risk (Gleason score =< 6, clinical stage < T2a, and PSA < 10) prostate cancer undergoing active surveillance who are re-biopsied and found to have intermediate risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure
Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
Intermediate risk prostate cancer patients will be eligible for this study; intermediate risk grouping will be assessed per National Comprehensive Cancer Network (NCCN) guidelines as: \r\n* Pathologically-proven diagnosis of prostate adenocarcinoma\r\n* PSA 10-20 ng/mL or\r\n* Gleason = 7 or\r\n* Clinical stage T2b/c
Participants must have the following features:\r\n* Intermediate-risk disease defined as Gleason 4+3 = 7 disease OR\r\n* High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/mL OR T3 disease (by prostate MRI)
Participants must have histologically confirmed malignancy and are candidates for external beam radiation therapy; patients eligible for this study must have intermediate risk disease defined as PSA values between 10-20 ng/ml and/or T2b-c and/or Gleason grade 7; if all three are present, less than 50% of the core biopsies can be positive
Patients previously diagnosed with low risk (Gleason score < 6, clinical stage < T2a, and PSA < 10) prostate cancer undergoing active surveillance who are re-biopsied and found to have intermediate risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure
Diagnosed with prostate cancer, T1-T2bN0M0 Gleason score (GS) 6-7; prostate specific antigen (PSA) < 20
Patients must have undergone a radical prostatectomy (any surgical technique is permitted) within 3 months from study entry and have high-risk disease define by any of the following:\r\n* Pathological stage T3a, T3b, T4 (any grade or initial prostate-specific antigen [iPSA])\r\n* Gleason sum >= 8 (any stage or iPSA)\r\n* Initial pre-operative PSA >= 20 ng/mL (any Gleason score [GS] or pT stage)\r\n* Any stage/PSA/Gleason patients with a 35% or greater chance of biochemical failure at 5 years based on Kattan's nomogram\r\n* Patients with lymph node (LN) positive disease, regardless of iPSA, pT stage or GS provided their post-operative PSA 6-8 weeks after surgery is =< 0.4 ng/mL (lymph node dissection is desired but not mandated)
All patients must meet one or more of the following disease features: clinical stage >= T3; primary Gleason score of 4 OR Gleason score of 8, 9 or 10; serum PSA >= 20 ng/mL; prostate magnetic resonance imaging (MRI) findings consistent with T3 disease; any clinical stage and PSA > 10 and Gleason score 7; a Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of < 60%
Adenocarcinoma of the prostate with locally advanced prostate cancer without distant metastatic with unfavorable risk features that are defined below: \r\n* Gleason Score >= 8; prostate-specific antigen (PSA) any; T-Stage any\r\n* Gleason Score 7; PSA >= 20; T-Stage any\r\n* Gleason Score 7; PSA any; T-Stage T3/T4
Biopsy proven intermediate risk prostate cancer, which includes patients with any one of the following variables:\r\n* Gleason 7 disease\r\n* Prostate-specific antigen (PSA) 10-20 ng/ml\r\n* Clinical T2b-T2c disease\r\n* Note: Patients who only have radiographic evidence of T3 disease (i.e. extracapsular extension, or seminal vesical invasion radiographically) will not be excluded
Patients must have either:\r\n* A Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of < 60%; please note that for the purposes of the nomogram calculation, the pre-biopsy prostate specific antigen (PSA) value must be used OR\r\n* Prostate biopsy Gleason sum >= 8 \r\n(NOTE: the Kattan nomogram probability must be calculated for all patients, including those eligible based on Gleason sum >= 8 only)
Low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 mg/mL
Histologically confirmed intermediate- to high-risk prostate adenocarcinoma (T1c-T3b, PSA > 10, and/or Gleason score >= 7) who have a greater than 15% risk of lymph node involvement as determined by the Roach equation
Prostate biopsy must be positive for cancer: clinically localized T1c or T2a, PSA =< 10, Gleason =< 6 at the time of initial diagnosis; as the intent of serial biopsy is to ensure that the disease has not progressed to the stage or grade of requiring treatment, the presence of a negative biopsy following an initial positive biopsy (coupled with clinically localized T1c or T2a PSA =< 10 and Gleason =< 6 for a patient who has had no treatment) will not render the patient ineligible; if the consecutive biopsy is either negative, or if positive and remains clinically localized T1c or T2a, PSA =< 10 and Gleason =< 6, the patient is eligible
Localized prostate cancer with at least one of the following National Comprehensive Cancer Network (NCCN) high-risk features:\r\n* Gleason sum >= 8\r\n* PSA > 20 ng/mL\r\n* Clinical stage >= T3
Patients must be candidates for short or long term androgen deprivation in combination with external beam radiation therapy (RT) based on the following criteria:\r\n* Intermediate risk disease: T2b/c, or Gleason 7, or prostate-specific antigen (PSA) 10-20\r\n* High risk disease: Gleason 8-10, or PSA > 20, or T3/4
Intermediate risk prostate cancer patients will be eligible for this study; risk groups will be assigned as per National Comprehensive Cancer Network (NCCN) guidelines; intermediate risk patients will be defined as:\r\n* PSA 10-20 ng/ml or\r\n* Gleason score = 7 or\r\n* Clinical stage T2b/T2c
prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
Patients must have the following features:\r\n* Gleason >= 4+3 = 7 OR\r\n* Gleason 3+4 = 7 AND at least one of the following: PSA > 20 ng/mL, or T3 disease (as determined by MRI)
Histologically confirmed adenocarcinoma of the prostate, clinically localized, low or low-intermediate risk disease (T1C/T2a, Gleason =< 7 [3+4], prostate-specific antigen [PSA] < 20)
A priori, we will allow men with concurrent benign prostatic hyperplasia (prostate volume > 50 g) to have a PSA between 10-15 ng/ml; and include men with low volume Gleason 3+4 disease, because such men have similar outcomes on active surveillance to those with Gleason =< 3+3
No restrictions on stage of cancer, Gleason score, and pre-treatment prostate-specific antigen (PSA) level
Must have one or more of the following:\r\n* pT3b or pT4 primary tumor\r\n* Gleason score 8-10\r\n* pN1 lymph node disease\r\n* Positive surgical margins\r\n* Pre-operative PSA of >= 10 ng/mL
Participants must have had a standard-of-care biopsy within 13 months of the baseline study visit and must have been diagnosed with low-grade, clinically localized prostate cancer (Gleason score =< 3+3 with a PSA at baseline < 10 ng/ml in participants < 70 years of age, OR Gleason score =< 3+4 with a PSA at baseline =< 15 ng/ml in participants >= 70 years of age); eligible participants will be those men who are able and willing to undergo AS with PSA monitoring and a scheduled biopsy performed at the end of the study
At least high risk prostate cancer defined by NCCN Guidelines Version 3.2016 (clinical stage ?T3a or PSA >20 ng/mL or Gleason score ?8).
Intermediate to high-risk disease, defined as one of the following factors: PSA > 10, T2b or greater, or a Gleason score of 7 or greater
Intermediate to high-risk disease (as determined by elevated prostate specific antigen [PSA] [PSA > 10], tumor [T]-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)
Patients fit criteria for one of the following categories:\r\n* COHORT 1\r\n** Known localized high risk prostate cancer (PSA > 10, Gleason 8-10 or clinical stage > T2c) with evidence of disease on standard imaging or\r\n* COHORT 2\r\n** Nonspecific or no evidence of disease on standard imaging modality AND biochemical prostate cancer relapse with a PSA >= 0.2 ng/mL
Intermediate to high-risk disease (as determined by elevated PSA [PSA > 10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)
Prostate carcinoma patients at high risk for metastasis with prostate–specific antigen (PSA) more than 20 ng/ml and/or Gleason score = 8/ > 8.
High-risk or very-high risk prostate cancer eligible for standard of care surgery\r\n* At least clinical T3a disease, and/or Gleason >= 8, and/or PSA > 20, as per clinical assessment and routine guidelines
Unfavorable risk intermediate prostate cancer eligible for standard of care surgery\r\n* Grade group 2 (Gleason score 3+4) with either PSA 10 - < 20 or clinical stage T2b-c, OR grade group 3 (Gleason 4+3) with PSA < 20
Intermediate to high-risk disease (as determined by elevated PSA [PSA > 10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)
Patients must have histopathology confirmed prostate cancer that is Gleason score =< 7 (4+3) clinical stage =< T2aN0M0 with a PSA below 15 ng/mL
Intermediate to high-risk disease (as determined by elevated prostate-specific antigen [PSA] [PSA > 10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or other risk factors)
Must have previously untreated (with definitive therapy) prostate cancer with intermediate or high risk features defined as:\r\n* Intermediate risk:\r\n** Prostate specific antigen (PSA) level is between 10 and 20 ng/ml or\r\n** Gleason score is 7 or\r\n** Stage T2b or T2c\r\n* High risk:\r\n** Gleason 8 and higher OR\r\n** PSA > 20 at the time of diagnosis OR\r\n** Seminal vesicle involvement OR\r\n** Possible (on magnetic resonance [MRI]) extra-capsular extension (T3 disease)
Newly diagnosed high-risk, localized or locally advanced prostate cancer pathologically proven by prostate biopsy within the past 12 months:\r\n* Clinical T3 or greater, or\r\n* PSA > 20 ng/ml, or\r\n* Clinically N1, or\r\n* Prostate biopsy histology grade ? Gleason 8-10
INCLUSION CRITERIA (NEXT 60 PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER): Pathologically confirmed clinically localized intermediate risk or higher prostate cancer (clinical stage >= T2b or Gleason sum >= 7 or PSA >= 10 ng/mL)
Patients with moderate to high-risk disease as defined by D' Amico risk stratification and having at least one of the following:\r\n* Prostate-specific antigen (PSA) level > 10 ng/ml\r\n* Gleason score >= 7\r\n* Clinical stage >= T2c
Intermediate or high risk prostate cancer (clinical tumor stage T2b or higher, Gleason 7 or higher, or PSA greater than 10); previously obtained MR imaging may be used for clinical T staging (extracapsular extension, seminal vesicle invasion)
National Comprehensive Cancer Network (NCCN) high risk disease (cT3 or Gleason score 8-10 or prostate specific antigen [PSA] > 20)
Candidates with prostate specific antigen (PSA) greater than 20, digital rectal exam consistent with disease outside the prostate (clinical T3/T4 disease), or Gleason score 8 or greater, should have a bone scan and diagnostic pelvic CT or MRI to exclude metastatic disease; these must be performed within 90 days of registration
Clinical criteria required to be eligible: \r\n* One of the following: \r\n** Pre-treatment prostate specific-antigen (PSA) >= 10 ng/dL, OR \r\n** Clinical T-stage assessed by digital rectal exam of >= T2a, OR\r\n** Radiographic >= T3a on MRI, OR \r\n** Gleason score of >= 3+4=7 \r\n* Visible intraprostatic tumor foci >= 1 cm in largest dimension on T2-weighted images based on initial pre-treatment MRI
INCLUSION CRITERIA:\n\n          -  Ability to provide informed consent and willingness to comply with protocol\n             requirements\n\n          -  Life expectancy ? 6 months\n\n        Cohort A only:\n\n          -  A diagnostic trans-rectal ultrasound (TRUS)-guided biopsy within 12 months of\n             enrollment showing adenocarcinoma of the prostate gland\n\n          -  Within 90 days of consent, serum PSA ? 15.0 ng/mL or ? 7.5 ng/mL if on 5 ?-reductase\n             inhibitors.\n\n          -  Candidates for active surveillance and/or a Gleason score ?3+4\n\n          -  Scheduled to undergo radical prostatectomy (RP) with or without pelvic lymph node\n             dissection (PLND)\n\n        Cohort B only:\n\n          -  Very low risk (VLR) prostate cancer defined by 2016 NCCN Guideline criteria:\n\n          -  T1c stage, and\n\n          -  PSA < 10 ng/mL, and\n\n          -  Gleason score ? 6 with < 3 biopsy cores cancer positive and ? 50% cancer in any core\n             based on prior prostate biopsy within 24 months of enrollment, and\n\n          -  PSA density < 0.15 mg/mL/g\n\n          -  Scheduled to undergo a reassessment of prostate cancer staging that includes prostate\n             biopsy as part of routine follow-up\n\n        EXCLUSION CRITERIA:\n\n          1. Subjects administered a radioisotope within 5 physical half-lives prior to study drug\n             injection.\n\n          2. Previous treatment with hormonal therapy, surgery (except biopsy), radiation therapy,\n             LHRH analogs, and non-steroidal anti-androgens, for the treatment of prostate cancer\n             or benign prostatic hyperplasia (BPH)\n\n          3. Planned androgen or anti-androgen therapy prior to RP surgery or biopsy\n\n          4. Subjects with any medical condition or other circumstances that, in the opinion of the\n             investigator, would significantly interfere with obtaining reliable data, achieving\n             study objectives, or completing the study\n\n          5. Malignancy (not including curatively treated basal or squamous cell carcinoma of the\n             skin) within the previous 5 years. (Ta stage transitional cell carcinoma bladder\n             cancer with negative surveillance cystoscopy within the past 2 years may be included).
Patients with clinically localized adenocarcinoma of the prostate who are scheduled to undergo radical prostatectomy (RP) with curative intent and have any the following clinico-pathologic features: (1) Gleason score sum >= 4+3 or any Gleason 5, (2) PSA > 20, and/or (3) clinical stage >= T3a (staging by magnetic resonance imaging [MRI] is allowed)
At least 2 of the following 3 factors: Gleason score(GS) 3+4=7 and/or PSA 10-20 and/or T2b/c
Greater than 50% of biopsy cores positive and at least one other risk factor: Gleason score (GS) 7 and/or PSA 10-20 and/or T2b/c
Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)\r\n* Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measure
Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)\r\n* Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (second [2nd] beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measure
Patients must have histologically or cytologically confirmed prostate cancer with a Gleason score available or interpretable; patients must have prostate cancer deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation and anti-androgen withdrawal when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 28 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 28 days prior to initial administration of drug for PSA evaluation and within 42 days for imaging studies (e.g, bone scans)\r\n* NOTE: rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA is required to be taken and be greater than the second measure; measurable disease is not required
Patients must have CaP deemed to be castration-resistant by one or more of the following criteria (despite androgen deprivation when applicable):\r\n* Progression of unidimensionally measurable disease assessed within 42 days prior to initial administration of drug\r\n* Progression of evaluable but not measurable disease assessed within 42 days prior to initial administration of drug for PSA evaluation and for imaging studies (e.g, bone scans)\r\n* Rising PSA, defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) should be taken at least 7 days after the reference value; a third confirmatory PSA measure (2nd beyond the reference level) should be greater than the second measure, and it must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA measurement is required to be taken and be greater than the second measure
Inclusion Criteria: (Dose-Escalation Phase)\n\n          1. For the dose-escalation phase, patients must have cytologically or histologically\n             proven advanced malignant solid tumors, with emphasis on CRPC.\n\n          2. Patients must be 18 years of age or older.\n\n          3. Patients must have a Zubrod (ECOG) performance status of 0-2.\n\n          4. Patients must have an estimated survival of at least 3 months.\n\n          5. Any prior chemotherapy must have been completed at least 4 weeks prior to start of\n             treatment. Prior radiation must have been completed at least 2 weeks prior to start of\n             therapy. Patients must have recovered from acute reversible side effects of prior\n             chemotherapy regimens or radiotherapy to < grade 1 (excluding alopecia, lymphopenia,\n             and hyperglycemia) according to the National Cancer Institute Common Terminology\n             Criteria for Adverse Events (NCI-CTCAE), version 4.0.\n\n          6. Radiographs (Xrays, CT scans, etc) to follow disease response or progression must have\n             been completed within 28 days prior to registration.\n\n          7. Patients must have adequate renal function as documented by a calculated creatinine\n             clearance of > 45 ml/min (see Appendix for formula for calculating creatinine\n             clearance).\n\n          8. Patients must have adequate liver functions: AST and ALT < 2.5 X upper limit of\n             normal, and bilirubin < upper limit of normal.\n\n        Inclusion Criteria: MTD Expansion Phase Cohort 1 - CRPC\n\n          1. All patients must have a histologic diagnosis of adenocarcinoma of the prostate which\n             is measurable or non-measurable.\n\n          2. Patients must have metastatic prostate cancer deemed to be unresponsive or refractory\n             to hormone therapy by one or more of the following (despite androgen deprivation and\n             antiandrogen withdrawal when applicable):\n\n               -  Progression of measurable disease assessed within 28 days prior to registration.\n\n               -  Progression of non-measurable disease assessed within 28 days prior to\n                  registration.\n\n               -  Rising PSA - Rising PSA is defined as at least two consecutive rises in PSA to be\n                  documented over a reference value (measure 1). The first rising PSA (measure 2)\n                  must be taken at least 7 days after the reference value. A third confirmatory PSA\n                  measure is required (2nd beyond the reference level) to be greater than the\n                  second measure, and it must be obtained at least 7 days after the 2nd measure. If\n                  this is not the case, a fourth PSA is required to be taken and be greater than\n                  the second measure. The patient must have a PSA ? 5 ng/ml in addition to\n                  increasing PSA to be eligible by rising PSA criteria alone. However, no minimum\n                  PSA is required for patients whose progression is based on measurable or\n                  non-measurable disease.\n\n          3. All patients must have a pre-study PSA obtained within 28 days prior to registration.\n\n          4. All patients must have had imaging studies within 28 days prior to registration. The\n             choice of imaging studies to follow disease will be at the discretion of the\n             investigator.\n\n          5. Patients must be offered the opportunity to participate in specimen banking for future\n             use (to include the serum and tissue correlative studies).\n\n          6. Patients must have been surgically or medically castrated. If method of castration is\n             LHRH agonists (leuprolide or goserelin) or LHRH antagonists, then the patient should\n             be willing to continue the use of LHRH agonists. Patients who have stopped treatment\n             should be willing to restart.\n\n          7. If the patient has been treated with non-steroidal antiandrogens (flutamide,\n             bicalutamide, nilutamide or ketoconazole), they must have been stopped at least 14\n             days prior to registration for ketoconazole and at least 28 days prior to registration\n             for flutamide, bicalutamide or nilutamide and the patients must have demonstrated\n             progression.\n\n          8. Prior, planned, or ongoing bisphosphonate therapy or denosumab is allowed.\n\n        Exclusion Criteria:\n\n        (Dose-Escalation Phase)\n\n          1. Pregnant or breastfeeding women. The effects of these drugs on the unborn fetus are\n             unknown. Documentation of a negative serum pregnancy test is required for all women of\n             reproductive potential.\n\n          2. Patient has a clinically significant concurrent illness. Patients must not have a\n             serious intercurrent medical or psychiatric illness, including serious active\n             infection.\n\n          3. Patient is currently enrolled in a different clinical study in which investigational\n             procedures are performed or investigational therapies are administered. Also, a\n             patient may not enroll in such clinical trials while participating in this study.\n\n          4. Patient has a history of allergy or hypersensitivity to the study drugs or a taxane.\n\n          5. Patient has serious medical risk factors involving any of the major organ systems such\n             that the investigator considers it unsafe for the patient to receive an experimental\n             research drug.\n\n          6. Prior therapy with ADI-PEG 20 or docetaxel.\n\n          7. Allergy to pegylated compounds or study drugs.\n\n        Exclusion Criteria: MTD Expansion Phase Cohort 1 - CRPC\n\n          1. Patient has a clinically significant concurrent illness. Patients must not have a\n             serious intercurrent medical or psychiatric illness, including serious active\n             infection.\n\n          2. Patient is currently enrolled in a different clinical study in which investigational\n             procedures are performed or investigational therapies are administered. Also, a\n             patient may not enroll in such clinical trials while participating in this study.\n\n          3. Patient has a history of allergy or hypersensitivity to the study drug or a taxane.\n\n          4. Patient has serious medical risk factors involving any of the major organ systems such\n             that the investigator considers it unsafe for the patient to receive an experimental\n             research drug.\n\n          5. Prior therapy with ADI-PEG 20 or docetaxel.\n\n          6. Allergy to pegylated compounds.
Patients must have rising serum PSA level defined as at least 2 consecutive rises in PSA documented over a reference value; the first rising PSA (2nd measure) should be taken at least 14 days after the reference value; a confirmatory PSA measure (3rd measure) obtained at least 14 days after the 2nd measure is required and must be greater than the 2nd measure; initial (reference) PSA must be >= 4 and the two consecutive rises must all be >= 0.5 over the previous PSA measure