This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has spread to other places in the body (metastatic) and has become resistant to testosterone-deprivation therapy (castration-resistant). Enzalutamide helps fight prostate cancer by blocking the use of testosterone by the tumor cells for growth. Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as rucaparib, fight prostate cancer by prevent tumor cells from repairing their DNA. Giving enzalutamide and rucaparib may make patients live longer or prevent their cancer from growing or spreading for a longer time, or both. It may also help doctors learn if a mutation in any of the homologous recombination DNA repair genes is helpful to decide which treatment is best for the patient.
PRIMARY OBJECTIVES: I. To compare radiographic progression-free survival (rPFS) and overall survival (OS) with enzalutamide and rucaparib camsylate (rucaparib) versus enzalutamide alone for patients with metastatic castration resistant prostate cancer commencing first-line therapy. II. (PK substudy) To evaluate the safety and tolerability of rucaparib and enzalutamide combination III. (Quality of life substudy) To compare quality of life as measured by FACT-P Trial Outcome Index in patients with mCRPC who receive enzalutamide plus rucaparib vs enzalutamide alone at the 12-month time point (primary QOL timepoint). SECONDARY OBJECTIVES: I. To compare rPFS and OS with enzalutamide and rucaparib versus enzalutamide alone within homologous-recombination repair (HRR) aberrant and wild-type patients. II. To evaluate the effects of concurrent administration of rucaparib on time to unequivocal clinical progression. III. To evaluate the effects of concurrent administration of rucaparib on best radiographic response using Prostate Cancer Working Group 3 (PCWG3) criteria. IV. To evaluate the effects of concurrent administration of rucaparib on duration of overall response. V. To evaluate the effects of concurrent administration of rucaparib on prostate specific antigen (PSA) response rate. VI. To evaluate the effects of concurrent administration of rucaparib on best response by serum PSA by months 7 and 13. VII. To evaluate the effects of concurrent administration of rucaparib on time to first symptomatic skeletal event (SSE). VIII. To evaluate the effects of concurrent administration of rucaparib on safety and tolerability as measured by National Cancer Institute (NCI) Common Toxicity Criteria; and trial discontinuation for treatment emergent toxicities. IX. To compare performance of plasma-based and tissue-based genomic profiling in detection of homologous-recombination repair mutation (HRRm) in metastatic castration-resistant prostate cancer (mCRPC). OUTLINE: In the randomized, placebo-controlled phase III study, patients will be randomized to 1 of 2 arms: ARM I: Patients will receive enzalutamide orally (PO) once daily (QD) and rucaparib PO twice daily (BID). Patients who did not undergo bilateral orchiectomy will also receive androgen deprivation therapy (ADT) consisting of leuprolide acetate intramuscularly (IM), goserelin acetate subcutaneously (SC) every 12 weeks or degarelix SC. Cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients will receive enzalutamide PO QD and placebo PO BID. Patients who did not undergo bilateral orchiectomy will also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles will repeat every 28 days in the absence of disease progression or unacceptable toxicity. After the completion of study treatment, patients will be followed every 3 months for 2 years, then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
61
Given PO
Given PO
Given PO
Given IM
Given SC
Given SC
Ancillary studies
Ancillary studies
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Radiographic progression-free survival (rPFS)
Radiographic progression-free survival (rPFS) is defined as the time from randomization to date of disease progression or death due to any cause. rPFS time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.
Time frame: Up to 5 years post treatment
Overall survival (OS)
Overall survival is defined as the time from randomization to death due to any cause. Overall survival time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.
Time frame: Up to 5 years post treatment
Radiographic progression-free survival (rPFS) within HRRm status
Defined as the time from randomization to date of disease progression or death due to any cause. rPFS time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.
Time frame: Up to 5 years post treatment
Time to unequivocal clinical progression
Defined as deterioration in clinical status clearly attributable to prostate cancer progression with occurrence of cancer pain requiring initiation of chronic administration of opiate analgesia, or an immediate need to re-initiate cytotoxic chemotherapy, radiation therapy or surgical intervention for disease-progression related events; or deterioration of Eastern Cooperative Oncology Group (ECOG) performance status to 3 or greater. Time to unequivocal clinical progression will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.
Time frame: Up to 5 years post treatment
Overall survival by HRRm status
Defined as the time from randomization to death due to any cause.Overall survival time will be compared between the treatment arms using a stratified (by HRRm status) log-rank test. Median times per treatment arms/HRRm status will be reported.
Time frame: Up to 5 years post treatment
Overall response rate
Defined as confirmed radiographic complete response or partial response. The proportion of patients with confirmed radiographic response or partial response will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).
Time frame: Up to 1 year after completion of treatment
Duration of overall response
Defined as the time from documentation of a radiographic response to disease progression. Duration of response time will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.
Time frame: Up to 1 year after completion of treatment
Prostate specific antigen (PSA) response rate
Defined as \>= 50% reduction in PSA from baseline. The proportion of patients with PSA response will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).
Time frame: Up to 1 year after completion of treatment
Best response by serum prostate specific antigen (PSA)
Defined as best percentage PSA decline from baseline to 7 and 13 months. The percent PSA decline will be compared between treatment arms with a Wilcoxon rank sum test.
Time frame: At 7 and 13 months from the start of treatment
Time to first symptomatic skeletal event (SSE)
Defined as the time to first use of external-beam radiation therapy to relieve skeletal symptoms, new symptomatic pathologic vertebral or nonvertebral bone fractures, spinal cord compression, or tumor-related orthopedic surgical intervention. Time to first SSE will be compared between the treatment arms using a log-rank test. Median times per treatment arms will be reported.
Time frame: Up to 5 years after completion of treatment
Incidence of adverse events
Frequency as measured by National Cancer Institute (NCI) Common Toxicity Criteria. The proportion of patients experiencing at least one grade 3+ adverse event will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).
Time frame: Up to 1 year after completion of treatment
Discontinuation for treatment emergent toxicities
The proportion of patients who discontinued treatment for emergent toxicities will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).
Time frame: Up to 1 year after completion of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Anchorage Oncology Centre
Anchorage, Alaska, United States
Katmai Oncology Group
Anchorage, Alaska, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, United States
...and 404 more locations