A Phase I Trial of Enzalutamide Plus the Glucocorticoid Receptor Antagonist CORT-125134 (Relacorilant) for Patients With Metastatic Castration Resistant Prostate Cancer (CRPC)
Condition: Prostate Cancer
Study Type: Interventional
Clinical Trials Identifier NCT 8-digits: NCT03674814
Sponsor: University of Chicago
Phase: Phase 1
Eligibility:
- Age: minimum 18 Years maximum N/A
- Gender: Male
Inclusion Criteria:
- 1. Histologically or cytologically confirmed prostate cancer with documented metastatic disease 2. Evidence of castrate testosterone level <50ng/dl (or surgical castration) 3. Evidence of disease progression:
- 2 or more new lesions on bone scan or
- Progressive disease on CT/MRI according to Response Evaluation Criteria in Solid Tumors 1.1 criteria or
- Rising Prostate Specific Antigen (PSA): PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart. 4. Prior treatment with at least one line of potent androgen receptor signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide) in either castration-sensitive or castration-resistant setting. 5. Any prior therapy for castrate disease is acceptable except prior GR antagonist treatment (e.g. mifepristone or relacorilant). 6. Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug. 7. Denosumab or zoledronic acid are allowed. 8. ECOG performance status ≤ 2. 9. Patients must have normal hepatic function as defined below:
- Total bilirubin
- AST(SGOT)/ALT(SGPT)
- Albumin >/=3.0 g/dL 10. Patients must have normal bone marrow function as defined below:
- Platelet count (plt) >/= 80,000 /microliter
- Hemoglobin (Hgb) >/= 9 g/dL
- Absolute neutrophil count (ANC) >/= 1500 11. Patients must have normal renal function as defined below:
- GFR >/= 30 mL/min 12. Ability to understand and the willingness to sign a written informed consent document. 13. Patients with active Diabetes Mellitus on glucose lowering medications are eligible provided they agree to and are able to self-monitor daily blood glucose levels due to potential risk of lowering glucose levels on relacorilant. 14. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:
- Condom (barrier method of contraception); AND
- One of the following is required: 1. Established use of oral, or injected or implanted hormonal method of contraception by the female partner; 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; 3. Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner; 4. Tubal ligation in the female partner; 5. Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy), for more than 6 months.
Exclusion Criteria:
- Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid within 2 weeks prior to first dose of study drug. a.Patients who have been on systemic corticosteroids with prednisone equivalent of 10mg or greater for greater than 3 months immediately prior to participation in this study must have documented ability to tolerate cessation of corticosteroids prior to enrollment.
- Inability to swallow capsules or known gastrointestinal malabsorption.
- Evidence of visceral disease on imaging in a patient who is an appropriate candidate for cytotoxic chemotherapy (docetaxel or cabazitaxel).
- History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 malignancies who are without evidence of disease, or other cancers curatively treated with no evidence of disease for > 5 years from enrollment.
- Blood pressure that is not controlled despite > 2 oral agents (SBP >160 and DBP >90 documented during the screening period with no subsequent blood pressure readings >160/100).
- History of seizure disorder or active use of anticonvulsants. Medications used to treat neuropathic pain such as gabapentin or pregabalin are allowed.
- Documented history of or current brain metastases due to seizure risk
- Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled.
- Active psychiatric illness/social situations that would limit compliance with protocol requirements.
- NYHA class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure).
- Concurrent therapy with strong inhibitors or inducers of CYP3A4 or CYP2C8 (See Section 9.12below for list of strong inhibitor or inducers) due to concerning possible drug-drug interactions
- Presence of concurrent medical conditions requiring systemic glucocorticoids for immunosuppression (e.g. Autoimmune diseases, organ transplantation) that is active and has required glucocorticoids in the last 6 months.
View trial on ClinicalTrials.gov