Trial Outcomes & Findings for Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations (NCT NCT04042831)

Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations

A patient is defined as a success if the patient is progression-free and alive at the first disease evaluation scan. Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria. The PFS rate will be calculated as the proportion of evaluable patients who are progression-free and alive at the first disease assessment scan. The final PFS rate point estimate and corresponding 95% confidence interval (CIs) will be reported according to the method of Clopper-Pearson.

Patients who are still alive at the time of analysis will be censored at the time of their last study assessment (if still actively on the study) or at the date, the patient was last known to be alive (if in survival follow-up). OS will be estimated using the Kaplan-Meier method. The median OS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported.

Progression free survival is defined as the time from study registration to disease progression or death, whichever occurs first. Disease progression will be determined based on RECIST 1.1 criteria. Patients who do not experience disease progression or death while on the protocol will be censored at their last disease assessment date. PFS will be estimated using the Kaplan-Meier method. Median PFS and corresponding 95% CIs (by Brookmeyer and Crowley) will be reported.

Objective response (unconfirmed) is defined as achieving a complete or partial response while on treatment. The objective response rate (ORR)\> will be calculated as the proportion of evaluable patients who achieve an objective response. Disease status will be assessed using RECIST v1.1\> criteria. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Will be defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier. The median DoR and corresponding 95% confidence interval will be reported.

Adverse events by patients will be summarized by frequencies and severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The proportion of patients who experience at least one grade 3+ adverse event (regardless of attribution) will be reported.

Will determine the prevalence of mutations including those targeting DNA repair pathways.

Will identify mutational signatures associated with pathogenic process in advanced biliary tract cancer samples. Genomic analyses will be performed on mandatory blood samples collected from\> patients at the start of therapy, every 8 weeks, and at progression.

Will correlate the presence of mutations and mutational signatures linked to mutations in DNA repair/HRR with clinical responses.

Will evaluate putative biomarkers related to: (a) de novo sensitivity and (b) tumor evolution and resistance, to PARP inhibition in biliary tract cancer.\> related to: (a) de novo sensitivity and (b)\> tumor evolution and resistance, to PARP inhibition in BTC.