Testing Two Oral Drugs Combination (Cediranib and Olaparib) Compared to a Single Drug (Olaparib) for Men With Advanced Prostate Cancer

Metastatic Prostate Carcinoma Clinical Trial

Official title: A Randomized Phase 2 Study of Cediranib in Combination With Olaparib Versus Olaparib Alone in Men With Metastatic Castration Resistant Prostate Cancer

Status Active, not recruiting

Clinical Trial Summary

This randomized phase II trial studies how well olaparib with or without cediranib works in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving olaparib and cediranib may help treat patients with castration-resistant prostate cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To assess the clinical activity of the combination of cediranib and olaparib, as measured by radiographic progression free survival (rPFS), as compared to olaparib monotherapy in patients with metastatic castration resistant prostate cancer (mCRPC).

SECONDARY OBJECTIVES:

I. To assess the clinical activity of the combination of cediranib and olaparib, as measured by prostate-specific antigen (PSA) response rate, radiographic response rate by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, and overall survival (OS), as compared to olaparib monotherapy in patients with mCRPC.

II. To evaluate association of homologous recombination deoxyribonucleic acid (DNA) repair deficiency (HRD) with the clinical activity of the combination of cediranib and olaparib or olaparib monotherapy, as measured by rPFS, in mCRPC patients.

III. To evaluate the safety the combination of cediranib and olaparib and olaparib monotherapy in patients with metastatic prostate cancer.

EXPLORATORY OBJECTIVES:

I. To characterize genomic alterations by whole exome sequencing in mCRPC patients and correlate that with clinical activity or resistance to olaparib with or without cediranib.

II. To characterize changes in ribonucleic acid (RNA) expression of DNA repair genes, angiogenesis markers, and immune markers, by whole transcriptome sequencing and correlate with clinical activity or resistance to olaparib with or without cediranib.

III. To characterize changes in immune tumor microenvironment in mCRPC patients by profiling expression of co-stimulatory and co-inhibitory molecules and tumor infiltrating lymphocytes, and correlate with clinical activity or resistance to olaparib with or without cediranib.

IV. To identify baseline predictive biomarkers for rPFS or response and to identify on-treatment markers of acquired resistance in men with mCRPC receiving either olaparib plus cediranib or olaparib alone.

V. To explore biomarker signatures that correlate with the clinical activity or resistance to olaparib with or without cediranib, including changes in gene expression or acquired mutations in tumor biopsies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive olaparib orally (PO) twice daily (BID) and cediranib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Prostate Adenocarcinoma With Neuroendocrine Differentiation
• Prostatic Neoplasms
• Stage IV Prostate Adenocarcinoma AJCC v7

• NCT number: NCT02893917
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 11, 2017
• Completion date: June 7, 2025