Opaganib and Androgen Antagonists for the Treatment of Patients with Metastatic Castration Resistant Prostate Cancer
- 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
- 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
- Urinalysis: no clinically significant abnormalities
- International normalized ratio (INR) =< 1.7
- 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
- New York Heart Association class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
- Underlying psychiatric disorder requiring hospitalization within the last two years
- Clinically significant neurological disorder (Parkinson’s disease, dementia, multiple sclerosis), as determined by the enrolling investigator
- Active, uncontrolled bacterial, viral or fungal infection, requiring systemic therapy
- Treatment with radiation therapy, surgery, or investigational therapy within 28 days prior to registration
- Unwillingness or inability to comply with procedures required in this protocol
- Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator
- Patients who are receiving coumadin, apixaban, argatroban or rivaroxaban. Patients who are receiving other drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with opaganib may be treated on this study with careful monitoring for toxic effects or loss of efficacy of the relevant drug
- Patients who are currently participating in any other clinical trial of an investigational product
- Other primary malignancy requiring systemic treatment within past 5 years except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer
- Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator
- Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
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.
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]) 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]).
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.
Trial Phase Phase II
Trial Type Treatment
Medical University of South Carolina
Michael Brian Lilly
- Primary ID 103193
- Secondary IDs NCI-2020-01752
- Clinicaltrials.gov ID NCT04207255