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

NCT04042831 | Unknown Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-ICRN-1702NCI-2019-04434P30CA015083
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 6

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.

Conditions

Bile Duct Adenocarcinoma; Fanconi Anemia Complementation Group Gene Mutation; Metastatic Bile Duct Carcinoma; PTEN Gene Deletion

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) at first scan

  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.

  At first scan (approximately 8 weeks)

Secondary Outcomes (5)

• 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

• Objective response rate

  Up to 3 years

• Duration of response (DoR)

  Up to 3 years

• Incidence of adverse events

  Up to 3 years

Other Outcomes (5)

• Prevalence of mutations

  Up to 3 years

• Mutational signatures

  Up to 3 years

• Presence of mutations and mutational signatures

  Up to 3 years

Study Arms (1)

Treatment (olaparib)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Olaparib

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood and tissue samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (olaparib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (olaparib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (olaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 2. (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)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 7 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer) (obtained =\< 7 days prior to registration)
• Serum creatinine =\< 1.5 x ULN (obtained =\< 7 days prior to registration)
• Institutional normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (obtained =\< 7 days prior to registration)
• Exception: Patients who are therapeutically treated with anticoagulant agents will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
• Alkaline phosphatase limit =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement of their cancer) (obtained =\< 7 days prior to registration)

You may not qualify if:

• 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) 5.0. (despite optimal medical management)
• History of or current pheochromocytoma
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =\< 6 months prior to registration
• Ongoing infection \> grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0
• Seizure disorder requiring medication
• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study =\< 28 days of registration and is clinically stable with respect to the tumor at the time of registration. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days prior to registration

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

COMPLETED

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

WITHDRAWN

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Bile Duct Neoplasms

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; olaparib

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Daniel H Ahn

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: August 2, 2019
• Study Start: June 24, 2020
• Primary Completion: August 30, 2024
• Study Completion: March 30, 2025
• Last Updated: October 13, 2023

Record last verified: 2023-07

Locations

US (6)