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Patients must be withdrawn from abiraterone for 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