Principal Investigator:Taplin, Mary-Ellen
Site Investigator(s):Constantine, Michael,
O'Connor, Thomas, P.
Site Research Nurse(s):Bretta, Katherine, v.
Cronis, Charles, Lewis
Freeman, Stefani, Danielle
Gundy, Kathryn, E.
Hixon, Nicole, R.
Pasquale, Kathryn, Mary
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.
- 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
- 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
- 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
- Prior chemotherapy for prostate cancer except if administered in neoadjuvant or
- 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
- 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
Protocol #: 17-384