Molecular Profiling of Advanced Biliary Tract Cancers

Study Overview
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Brief Summary
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Biliary tract cancer (BTC) accounts for <1% of all cancers, but remains a highly fatal malignancy. Surgical resection is the only hope for cure, but most patients present with advanced disease when curative-intent surgery is not possible. The therapeutic options for patients with advanced disease are limited, primarily to chemotherapeutic regimens, which are based on empiric evidence without the use of biomarkers. These current treatment strategies have been largely ineffective in controlling the disease, resulting in poor survival outcomes of less than 1 year. An understanding of the molecular characteristics of biliary tract cancer may enable stratification of patients into therapies that target specific molecular alterations with greater efficacies and improved clinical outcomes. This study aims to investigate the feasibility and clinical utility of prospective molecular profiling of advanced biliary tract cancer. The primary endpoint of this study is to demonstrate the feasibility of returning whole genome sequencing results within 8 weeks of tumour biopsy for second-line treatment consideration (n=30 patients). In parallel, tumour whole transcriptome sequencing will be performed to identify actionable molecular alterations (e.g., fusion transcripts). Once the primary endpoint is met, the study will be expanded. Current funding allows expansion to 40 patients in total.

Official Title
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Comprehensive Molecular Profiling of Advanced Biliary Tract Cancers for Better Treatment Selection: a McGill University Health Centre Study (COMPASS-B-MUHC)

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Other: Tumour and germline molecular profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a histological or radiological diagnosis of inoperable or metastatic BTC. Patient must have a tumour that is amenable to a core needle biopsy. Patients must have a measurable lesion by RECIST 1.1 in addition to the lesion that is going to be biopsied. Patients must be fit to safely undergo a tumour biopsy as judged by the investigator. Eastern Cooperative Group (ECOG) performance status ≤ 1. Life expectancy of greater than 90 days. Within 14 days of the proposed biopsy date, patients must have normal organ and marrow function. Patients must undergo systemic treatment with gemcitabine-based regimens as first-line standard systemic palliative treatment with or without other investigational agents within a clinical trial. Ability to understand and willing to sign a written informed consent document. Exclusion Criteria: Patients with one or more contraindications to tumour biopsy. Patients who have had any prior chemotherapy or other anti-cancer agent in the advanced stage setting. Patients who are currently on anti-cancer treatment. Patients with known brain metastases. Uncontrolled concurrent illness that would limit compliance with study requirements. Any other condition that would contraindicate the patient's participation due to safety concerns or compliance with clinical study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individuals with advanced biliary tract cancer<br>Following a tumour biopsy for molecular profiling, chemo-naive patients with advanced biliary tract cancer will receive first-line gemcitabine-based chemotherapy or an investigational drug on a participating clinical trial. | Other: Tumour and germline molecular profiling<br>* Tumour whole genome sequencing, germline whole genome sequencing, tumour whole transcriptome sequencing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with tumour whole genome sequencing returned within 8 weeks | We have estimated that 30 patients will be required to reach the primary end point, which will be met if we demonstrate that tumor whole genome sequencing data is available at 8 weeks from the tumour biopsy for 80% of patients. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | Number of patients that achieve stability of disease (cancer) by imaging (RECIST criteria) with first-line standard chemotherapy, consisting of gemcitabine backbone. | 4 years | 
| Progression-free survival rate | Progression free survival (PFS) defined as the interval between the date of registration and the earliest date of disease progression or death due to any cause of patients treated with 1st line chemotherapy. | 4 years | 
| Overall survival rate | Overall survival (OS) defined as the interval between the date of registration and the date of death of patients treated with 1st line chemotherapy. | 4 years | 
| Number of patients in whom at least 1 actionable mutation is identified | based on whole genome sequencing or RNA sequencing analyses. | 4 years | 
| Number of patients who received a targeted therapy (after first-line treatment) | based on the identification of an actionable mutation by whole genome sequencing or RNA sequencing. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biliary tract cancer, Cholangiocarcinoma, Molecular Profiling, Whole Genome Sequencing, Whole Transcriptome Sequencing