A Phase II Study of Olaparib in Patients With Advanced Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Bile Duct Adenocarcinoma
- Sponsor
- Academic and Community Cancer Research United
- Enrollment
- 36
- Locations
- 6
- Primary Endpoint
- Progression-free survival (PFS) at first scan
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This phase II trial studies how well olaparib works in treating patients with biliary tract cancer that has spread to other places in the body (metastatic) and with aberrant DNA repair gene mutations. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the efficacy (progression free survival \[PFS\] rate at first scan) of olaparib monotherapy in advanced biliary tract cancer (BTC) with mutations in deoxyribonucleic acid (DNA) repair genes. SECONDARY OBJECTIVES: I. To determine the overall survival of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib. II. To determine the progression free survival of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib. III. To determine the objective response of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib. IV. To assess the duration of response for patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib who experience an objective response. V. To assess the frequency and severity of adverse events in advanced biliary tract cancer patients treated with olaparib. CORRELATIVE RESEARCH OBJECTIVES: I. Determine the prevalence of mutations including those targeting DNA repair pathways. II. Identify mutational signatures associated with pathogenic process in advanced biliary tract cancer samples. III. Correlate the presence of mutations and mutational signatures linked to mutations in DNA repair genes and homologous recombinant repair with clinical responses to olaparib. IV. To evaluate putative biomarkers related to: Iva. De novo sensitivity. IVb. Tumor evolution and resistance, to PARP inhibition from olaparib in BTC. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) throughout the trial, and collection of blood and tissue samples on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>= 18 years
- •Histological or cytological documentation of metastatic adenocarcinoma of the biliary tract
- •Patients with previously identified genetic aberrations that are associated with homologous recombinant repair pathway will be eligible \[e.g. somatic mutations in ATM, ATR, CHEK2, BRCA 1/2, RAD51, BRIP1, PALB2, PTEN, FANC, NBN, EMSY, MRE11, ARID1A\] or germline mutations in the above genes. Clinical Laboratory Improvement Act (CLIA)-certified assays including commercial tests (Foundation Medicine, Caris, Tempus) will be allowed
- •Measurable disease
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to
- •(Form is available on the Academic and Community Cancer Research United \[ACCRU\] website)
- •Life expectancy of \>= 16 weeks per estimation of investigator
- •Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 7 days prior to registration)
- •Platelet count \>= 75,000/mm\^3 (obtained =\< 7 days prior to registration)
- •Hemoglobin \>= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =\< 7 days prior to registration)
Exclusion Criteria
- •Platinum refractory disease which was defined as:
- •Evidence disease progression on platinum based chemotherapy regimen or
- •Evidence of disease progression =\< 6 months of completion of platinum based adjuvant chemotherapy regimen
- •Patient has received prior systemic anti-cancer therapy, tumor embolization or radiotherapy =\< 28 days prior to registration
- •Major surgical procedure, open biopsy, or significant traumatic injury =\< 28 days prior to registration
- •NOTE: Patients must have recovered from any effects of any major surgery
- •Congestive heart failure - New York Heart Association (NYHA) \>= class II
- •Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg. unstable ischemia, uncontrolled symptomatic arrhythmia, corrected QT interval by Fridericia's correction formula \[QTcF\] prolongation \> 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome. Cardiac arrhythmias requiring anti-arrhythmic therapy.
- •NOTE: Pacemaker, beta blockers or digoxin are permitted
- •Uncontrolled hypertension - grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.
Arms & Interventions
Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial, and collection of blood and tissue samples on study.
Intervention: Biospecimen Collection
Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial, and collection of blood and tissue samples on study.
Intervention: Computed Tomography
Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial, and collection of blood and tissue samples on study.
Intervention: Magnetic Resonance Imaging
Treatment (olaparib)
Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial, and collection of blood and tissue samples on study.
Intervention: Olaparib
Outcomes
Primary Outcomes
Progression-free survival (PFS) at first scan
Time Frame: At first scan (approximately 8 weeks)
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.
Secondary Outcomes
- Objective response rate(Up to 3 years)
- Duration of response (DoR)(Up to 3 years)
- Incidence of adverse events(Up to 3 years)
- Overall survival (OS)(From study entry to death from any cause, assessed up to 3 years)
- PFS(From study entry to the first of either disease progression or death from any cause, assessed up to 3 years)