Prostate Cancer Clinical Trial
A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer
Summary
This is a randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer and PSA doubling time ≤ 9 months at the time of study entry.
Full Description
Patients will be stratified by PSA doubling time (< 3 months vs. 3-9 months) and randomized in 1:1:1 fashion to one of three treatment arms: (1) Control arm consisting of LHRH analogue monotherapy (degarelix or leuprolide), (2) Experimental arm consisting of apalutamide in combination with LHRH analogue, and (3) Experimental arm consisting of apalutamide, abiraterone acetate + prednisone, and LHRH analogue. Patients will be treated for a maximum duration of 52 weeks and then enter follow up phase until the time of PSA progression, development of metastasis, or patient withdrawal from study, whichever occurs first. Patients with PSA progression will be followed long term until the development of castration resistance, first metastasis, and death.
The primary endpoint of the study is PSA progression-free survival in the intent-to-treat patient population. PSA progression during the 52-week treatment period is defined as a rising PSA confirmed on repeat measurement, and at least 25% and 2 ng/mL above nadir or baseline, whichever is lower. PSA progression during follow up defined as PSA > 0.2 ng/mL confirmed by repeat measurement at least 2 weeks later. Secondary study endpoints include PSA progression-free survival in testosterone-evaluable population, 36-month PSA progression-free survival rate in both intent-to-treat and testosterone-evaluable populations, time to testosterone recovery, time to castration resistance, metastasis-free survival, quality of life, and safety. Each experimental arm will be compared against the control arm in pair-wise fashion. The study is not powered to detect differences in primary or secondary endpoints between the two experimental arms.
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed prostate adenocarcinoma
Prior radical prostatectomy
Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 6-12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to therapeutic interventions (e.g. salvage radiation) will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (https://www.mskcc.org/nomograms/prostate/psa-doubling-time)
Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient co-morbidities.
Screening PSA > 0.5 ng/mL
No definitive evidence of metastases on screening CT or MRI of abdomen/pelvis and radionuclide whole body bone scan per the judgment of the investigator. Abdominal and/or pelvic lymph nodes measuring 2 cm or less in short axis diameter are allowed. Lesions identified on other imaging modalities (e.g. PSMA or choline PET) that are not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on bone scan should be followed up with additional imaging as clinically indicated.
Screening serum testosterone > 150 ng/dL
Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1
Age ≥ 18 years
Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to cycle 1 day 1
Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
Adequate organ function as defined by the following laboratory values at screening:
Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < 2.5 x upper limit of normal (ULN)
Total serum bilirubin ≤1.5 x ULN. In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.
Estimated creatinine clearance > 45 ml/min using Cockroft-Gault equation
Platelets ≥ 100,000/microliter independent of transfusion and/or growth factors within 3 months prior to randomization
Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within 3 months prior to randomization
Serum albumin ≥ 3.0 g/dL
Exclusion Criteria:
Prior androgen deprivation therapy and/or first generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage setting before, during, and/or following radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is > 9 months prior to date of randomization and total duration of prior therapy is ≤ 36 months.
Prior treatment with CYP17 inhibitor (e.g. ketoconazole, abiraterone acetate, galeterone) or second generation androgen receptor antagonist including apalutamide or enzalutamide
Prior chemotherapy for prostate cancer except if administered in neoadjuvant or adjuvant setting
Use of 5-alpha reductase inhibitor within 42 days prior to cycle 1 day 1
Use of investigational agent within 28 days prior to randomization
Use of other prohibited medications within 7 days prior to cycle 1 day 1 on study (Arms B and C only)
Prior bilateral orchiectomy
Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
Uncontrolled hypertension
Gastrointestinal disorder affecting absorption or the ability to swallow tablets
Baseline severe hepatic impairment (Child-Pugh Class B & C)
Intercurrent illness that is not controlled such as active infection, psychiatric illness/social situations that would limit compliance with study requirements
Any chronic medical condition requiring a higher dose of corticosteroid than equivalent of 5 mg prednisone/prednisolone once daily
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There are 67 Locations for this study
Phoenix Arizona, 85054, United States
Chula Vista California, 91911, United States
Duarte California, 91010, United States
Fremont California, 94538, United States
Fresno California, 93703, United States
La Mesa California, 91942, United States
Mountain View California, 94040, United States
Palo Alto California, 94301, United States
Saint Helena California, 94574, United States
San Diego California, 92093, United States
San Diego California, 92123, United States
San Francisco California, 94158, United States
Santa Cruz California, 95065, United States
Sunnyvale California, 94086, United States
Washington District of Columbia, 20007, United States
Washington District of Columbia, 20007, United States
'Aiea Hawaii, 96701, United States
Honolulu Hawaii, 96813, United States
Chicago Illinois, 60601, United States
Chicago Illinois, 60637, United States
Evanston Illinois, 60201, United States
Maywood Illinois, 60153, United States
Quincy Illinois, 62301, United States
Urbana Illinois, 61801, United States
Wichita Kansas, 67214, United States
Brewer Maine, 04412, United States
Kennebunk Maine, 04043, United States
Scarborough Maine, 04074, United States
Topsham Maine, 04086, United States
Boston Massachusetts, 02215, United States
Milford Massachusetts, 01757, United States
South Weymouth Massachusetts, 02190, United States
Minneapolis Minnesota, 55455, United States
Saint Louis Park Minnesota, 55416, United States
Saint Louis Missouri, 63110, United States
Omaha Nebraska, 68114, United States
Las Vegas Nevada, 89106, United States
Concord New Hampshire, 03301, United States
Hooksett New Hampshire, 03106, United States
Basking Ridge New Jersey, 07920, United States
Middletown New Jersey, 07748, United States
Morristown New Jersey, 07962, United States
Albuquerque New Mexico, 87109, United States
Albuquerque New Mexico, 87131, United States
Las Cruces New Mexico, 88011, United States
Santa Fe New Mexico, 87505, United States
Buffalo New York, 14215, United States
Buffalo New York, 14263, United States
Commack New York, 11725, United States
Harrison New York, 11533, United States
New York New York, 10065, United States
New York New York, 10065, United States
New York New York, 10461, United States
Syracuse New York, 13210, United States
Chapel Hill North Carolina, 27514, United States
Charlotte North Carolina, 28204, United States
Salisbury North Carolina, 28144, United States
Winston-Salem North Carolina, 27157, United States
Centerville Ohio, 45459, United States
Columbus Ohio, 43210, United States
Toledo Ohio, 43623, United States
Tulsa Oklahoma, 74146, United States
Portland Oregon, 97213, United States
Portland Oregon, 97239, United States
Pittsburgh Pennsylvania, 15232, United States
Spartanburg South Carolina, 29303, United States
Houston Texas, 77030, United States
Marshfield Wisconsin, 54449, United States
Milwaukee Wisconsin, 53226, United States
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