GnRH analog, Abiraterone Acetate, and Prednisone in Treating Patients with Stage IV Castration Sensitive Prostate Cancer
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- > 75% PSA decline after 12 to 16 weeks of run in period with GnRH analog, and AR directed therapy
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be < 2.5 x upper limit of normal (ULN)
- Total bilirubin < 1.5 X ULN
- Estimated creatinine clearance must be > 40 mL/min
- Absolute neutrophil count (ANC) > 1500/l
- Hemoglobin above 9 g/dl
- Platelet count > 100,000/l
- Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 28 days prior to study enrollment
- Ability to give written informed consent
- Prior GnRH analog with GnRH analogue for non-metastatic prostate cancer within 12 months prior to study enrollment; or > 3 months of GnRH analog in the metastatic setting
- Prior treatments with TAK-700/Orteronel, ketoconazole, abiraterone, darolutamide, apalutamide or enzalutamide for more than 12 weeks
- Documented central nervous system metastases or liver metastasis
- Requiring opioids for cancer related pain
- Prior surgical castration
- Treatment with any investigational compound within 30 days prior to the first dose of study drugs
- Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
- Uncontrolled hypertension despite appropriate medical therapy (blood pressure of greater than 160 mmHg systolic and 100 mmHg diastolic during the screening period). Note: Patients may be rescreened after adjustments of antihypertensive medications
- Unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade > 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0), New York Association class III or IV heart failure
- Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C not contained with anti-viral therapy, life threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in investigator’s opinion, potentially interfere with participation in this study
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of study drugs, including difficulty swallowing tables
- Subjects with delayed healing of wounds, ulcers, and/or bone fractures
- Inability to comply with protocol requirements
I. Test the feasibility of adaptive antiandrogen therapy gonadotropin-releasing hormone analog (GnRH analog) in patients with asymptomatic high risk metastatic castration sensitive prostate cancer (mCSPC).
I. Assess the clinical benefits of adaptive GnRH analog by comparing to historical controls.
EXPLORATORY/CORRELATIVE STUDIES OBJECTIVES:
I. Detect the intra-tumor heterogeneity of androgen receptor (AR) and Cyp17 IHC stains on formalin-fixed paraffin-embedded (FFPE) blocks of prostate tumors and or metastatic lesions.
II. Refine the mathematical model for adaptive GnRH analog.
III. To develop imaging habitat biomarkers to track diseases progression using the patients’ computed tomography (CT) and bone scans and compare with conventional progression variables (like prostate specific antigen [PSA]).
IV. Compare the AR, Cyp17 immunohistochemistry (IHC) stains as well as imaging biomarkers with a retrospective cohort of mCSPC patients who underwent continuous GnRH analog as standard of care.
V. Detect and track the changes of AR mutations and AR amplification in tumor cell free deoxyribonucleic acid (DNA).
Patients receive standard of care gonadotropin-releasing hormone analog via injections and gonadotrophin releasing hormone (GnRH) such as leuprolide acetate, goserelin acetate, or triptorelin for 12-16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive gonadotropin-releasing hormone analog, abiraterone acetate orally (PO) daily, prednisone PO once daily (QD), enzalutamide PO daily, or apalutamide PO daily for 8-12 weeks in the absence of disease progression of unacceptable toxicity. Participants who PSA reaches 2 folds or higher of baseline PSA, may restart treatment.
After completion of study treatment, patients are followed up at 4-6 weeks.
Trial Phase Phase I
Trial Type Treatment
Moffitt Cancer Center
- Primary ID MCC-19367
- Secondary IDs NCI-2018-01095
- Clinicaltrials.gov ID NCT03511196