A Phase 3 Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer

Protocol # :
Prostate Cancer
Disease Sites
Principal Investigator
Taplin, Mary-Ellen
Site Investigator
Constantine, Michael
O'Connor, Thomas, P.
Site Research Nurses
Bretta, Katherine, v.
Caradonna, Lisa
Cronis, Charles, Lewis
Freeman, Stefani, Danielle
Gundy, Kathryn, E.
Healy, Erin, C.
Hixon, Nicole, R.
Katica, Dean
Lagerstedt, Elizabeth
Leisner, Claire
Mingrino, Sage
Pace, Amanda
Pasquale, Kathryn, Mary
Polinski, Karen
Porter, Kathryn
Prisby, Judith
Theodore, Catherine
Walsh, Meghara

Trial Description

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.

Eligibility Requirements

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

- 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

- 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