Opaganib and Androgen Antagonists for the Treatment of Patients with Metastatic Castration Resistant Prostate Cancer
103193 (primary)
NCI-2020-01752
Summary
This phase II trial studies how well opaganib works when added to androgen antagonists in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Opaganib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Testosterone can cause the growth of prostate cancer cells. Androgen antagonists, such as abiraterone and enzalutamide, may help fight prostate cancer by lowering the amount of testosterone made by the body, or by blocking the use of testosterone by the tumor cells. Giving opaganib with androgen antagonists may work better than androgen antagonists alone in treating patients with castration resistant prostate cancer.
Objectives
PRIMARY OBJECTIVE:
I. To measure the proportion of patients with disease control during opaganib (plus abiraterone or enzalutamide) therapy, using a composite metric based on prostate specific antigen (PSA), bone scan, and Response Evaluation Criteria in Solid Tumors (RECIST) measurements per Prostate Cancer Working Group 3 (PCWG3) criteria.
SECONDARY OBJECTIVES:
I. To estimate the overall survival (OS), radiographic progression-free survival (rPFS), and PSA progression-free survival (PSA-PFS) times in patients treated with opaganib (plus abiraterone or enzalutamide).
II. To document the PSA response rate, RECIST response rate, and change in quality of life (QOL) (Functional Assessment of Cancer Therapy- Prostate [FACT-P]) and pain score (Likert Pain Score) in metastatic castration resistant prostate cancer (mCRPC) patients treated with opaganib (plus abiraterone or enzalutamide) after four cycles of treatment.
III. To determine the effects opaganib on regression or progression of mCRPC clones with amplified AR or MYC, identified by serial circulating tumor deoxyribonucleic acid (ctDNA)-based genomic profiling.
IV. To assess safety of opaganib in mCRPC patients, in combination with abiraterone or enzalutamide, gonadotropin releasing hormone receptor (GnRHR) agonist/antagonist (this is the primary objective for the run-in cohort).
V. To monitor changes in numbers or activity of immune cells and myeloid-derived suppressor cells during opaganib therapy (with continued androgen-depleting therapy [ADT]).
OUTLINE:
Patients receive opaganib orally (PO) twice daily (BID). Patients also continue receiving abiraterone or enzalutamide. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 30 months.
Eligibility
- Patient must have mCRPC. Each patient must have:
* Tissue diagnosis documented by pathology report, or clinic note attesting to same
* Radiographically-demonstrated metastases
* Patients must have adenocarcinoma, or ductal carcinoma, or combinations of these two entities
- Voluntary, signed and dated, Institutional Review Board (IRB)-approved informed consent form in accordance with regulatory and institutional guidelines
- Documented progression during treatment with enzalutamide or abiraterone, as determined by the enrolling investigator
- Testosterone level documented to be less than 50 ng/dL
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Bilirubin =< 1.5 times upper limit of normal (Common Terminology Criteria for Adverse Events [CTCAE] grade 1 baseline)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) & alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x upper limit of normal (ULN) (CTCAE grade 1 baseline)
- Subjects with Gilbert’s syndrome may be included if the total bilirubin is < 3 x ULN and the direct bilirubin is within normal limits
- Serum creatinine =< 1.5 x ULN (CTCAE grade 1 baseline)
- Absolute neutrophil count >= 1000 cells/mm^3
- Platelet count >= 75,000 (plt/mm^3) (CTCAE grade 1 baseline)
- Hemoglobin >= 9.0 g/dL
- Fasting blood glucose of < 165 mg/dL or random blood glucose of < 200 mg/dL
- Urinalysis: no clinically significant abnormalities
- International normalized ratio (INR) =< 1.7 for patients not on anti-coagulation medications (meds)
- Well-controlled blood pressure as determined by the treating investigator
- Patients requiring narcotic analgesics must be on stable doses for at least 2 weeks prior to study entry
Treatment Sites in Georgia
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