Olaparib in Treating Patients With Metastatic or Advanced Urothelial Cancer With DNA-Repair Defects
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|ClinicalTrials.gov Identifier: NCT03375307|
Recruitment Status : Recruiting
First Posted : December 18, 2017
Last Update Posted : October 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Abnormal DNA Repair Advanced Urothelial Carcinoma Metastatic Urothelial Carcinoma Stage III Bladder Urothelial Carcinoma AJCC v6 and v7 Stage IV Bladder Urothelial Carcinoma AJCC v7||Drug: Olaparib||Phase 2|
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).
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.
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.
VIII. To determine the expression of Schlafen 11 (SLFN11) in tumor versus (vs.) stroma cells, and the potential tumor heterogeneity based on SLFN11 expression.
Patients receive olaparib orally (PO) twice daily (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 at 4 weeks, every 3 months for 1 year, and annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Olaparib (AZD2281) in Patients With Metastatic/Advanced Urothelial Carcinoma With DNA-Repair Defects|
|Actual Study Start Date :||August 3, 2018|
|Estimated Primary Completion Date :||August 21, 2023|
|Estimated Study Completion Date :||August 21, 2023|
Experimental: Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Overall response rate (ORR) as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ]ORR will be reported along with 95% exact confidence intervals.
- Progression free survival (PFS) [ Time Frame: From the date of olaparib initiation to investigator-assessed clinical progression or radiographic progression (by RECIST), or death from any cause, whichever occurs first, assessed up to 5 years ]PFS will be determined using a Kaplan-Meier curve, with probabilities at various time points indicated along with appropriate confidence intervals.
- Incidence of adverse events [ Time Frame: Up to 5 years ]Will be assessed according to the Common Terminology Criteria for Adverse Events version 5.0.
- Individual deoxyribonucleic acid (DNA)-repair defects [ Time Frame: Up to 5 years ]The association between individual DNA-repair defects and ORR will be determined using Fisher's exact test.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03375307
|United States, California|
|Los Angeles County-USC Medical Center||Suspended|
|Los Angeles, California, United States, 90033|
|USC / Norris Comprehensive Cancer Center||Suspended|
|Los Angeles, California, United States, 90033|
|USC Norris Oncology/Hematology-Newport Beach||Suspended|
|Newport Beach, California, United States, 92663|
|United States, Colorado|
|University of Colorado Hospital||Suspended|
|Aurora, Colorado, United States, 80045|
|United States, Kentucky|
|University of Kentucky/Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Site Public Contact 859-257-3379|
|Principal Investigator: Peng Wang|
|United States, Maryland|
|NCI - Center for Cancer Research||Suspended|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Andrea B Apolo||National Cancer Institute LAO|