A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma With DNA-Repair Defects
PRIMARY OBJECTIVES: I. To evaluate the efficacy of olaparib in two cohorts of patients with metastatic/advanced urothelial carcinoma (UC) pre-selected by deoxyribonucleic acid (DNA)-repair defects as measured by overall response rate (ORR). SECONDARY OBJECTIVES: I. To describe the effect of therapy...
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March 15, 2019
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Copyright: Last update posted on ClinicalTrials.gov: March 15, 2019
Copyright: Last updated: 2019-05-06
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- PRIMARY OBJECTIVES: I. To evaluate the efficacy of olaparib in two cohorts of patients with metastatic/advanced urothelial carcinoma (UC) pre-selected by deoxyribonucleic acid (DNA)-repair defects as measured by overall response rate (ORR). SECONDARY OBJECTIVES: I. To describe the effect of therapy on progression free survival (PFS). II. To describe the effect of therapy on overall survival (OS). III. To describe the safety/tolerability and drug-related toxicities of olaparib. TERTIARY OBJECTIVES: I. To determine the proportion of patients with DNA-repair pathway-mutated genes in metastatic UC (patient cohort referred for screening). II. To explore tumor-mutational profiles in metastatic tumor biopsies, saliva "normal" DNA, changes in tumor or peripheral immune characteristics, or tumor associated somatic mutation load in blood DNA in response to treatment. III. To explore changes in plasma cytokines and correlate with clinical response. IV. To correlate levels of circulating endothelial cells with clinical outcome. V. To correlate levels of circulating tumor cells (CTCs) with clinical outcome. VI. To correlate peripheral immune and DNA damage response transcriptional signatures with clinical outcomes. VII. To determine the effectiveness of using next-generation sequencing (NGS) to identify DNA-repair pathway gene defects in tumor samples and circulating DNA and identify patients with UC suitable for PARP inhibition. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 1 year, and annually thereafter.