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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Bibliographic Details
Other Involved Persons: National Cancer Institute (NCI)
Format: eBook
Language:English
Published: Bethesda (Maryland) : ClinicalTrials.gov March 15, 2019
Item Description:Copyright: Source: ClinicalTrials.gov (no modifications made)
Copyright: ClinicalTrials.gov processed this data on May 06, 2019
Copyright: Last update posted on ClinicalTrials.gov: March 15, 2019
Copyright: Last updated: 2019-05-06
Physical Description:Online-Ressource
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520 |a 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. 
653 2 |a Clinical Study 
653 2 |a Clinical Trial, Phase II 
653 2 |a Carcinoma 
653 2 |a Carcinoma, Transitional Cell 
653 4 |a Clinical Study Status: Recruiting 
653 4 |a Abnormal DNA Repair 
653 4 |a ATM Gene Mutation 
653 4 |a ATR Gene Mutation 
653 4 |a BAP1 Gene Mutation 
653 4 |a BARD1 Gene Mutation 
653 4 |a BLM Gene Mutation 
653 4 |a BRCA1 Gene Mutation 
653 4 |a BRCA2 Gene Mutation 
653 4 |a BRIP1 Gene Mutation 
653 4 |a CHEK1 Gene Mutation 
653 4 |a CHEK2 Gene Mutation 
653 4 |a FANCC Gene Mutation 
653 4 |a FANCD2 Gene Mutation 
653 4 |a FANCE Gene Mutation 
653 4 |a FANCF Gene Mutation 
653 4 |a MEN1 Gene Mutation 
653 4 |a Metastatic Urothelial Carcinoma 
653 4 |a MLH1 Gene Mutation 
653 4 |a MSH2 Gene Mutation 
653 4 |a MSH6 Gene Mutation 
653 4 |a MUTYH Gene Mutation 
653 4 |a NPM1 Gene Mutation 
653 4 |a PALB2 Gene Mutation 
653 4 |a PMS2 Gene Mutation 
653 4 |a POLD1 Gene Mutation 
653 4 |a POLE Gene Mutation 
653 4 |a PRKDC Gene Mutation 
653 4 |a RAD50 Gene Mutation 
653 4 |a RAD51 Gene Mutation 
653 4 |a SMARCB1 Gene Mutation 
653 4 |a Stage III Bladder Urothelial Carcinoma AJCC v6 and v7 
653 4 |a Stage IV Bladder Urothelial Carcinoma AJCC v7 
653 4 |a STK11 Gene Mutation 
653 4 |a Urothelial Carcinoma 
653 4 |a Klinische Studie 
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