CAnadian CAncers With Rare Molecular Alterations (CARMA) - Basket Real-world Observational Study (BROS)

Recruiting

• Conditions: Malignancies Multiple; Receptor Tyrosine Kinase Gene Mutation; Ras (Kras or Nras) Gene Mutation; Cancer; Molecular Sequence Variation; Cancer, Therapy-Related; Genetic Alteration; Malignant Solid Tumor; Gene Fusion; RTK Family Gene Mutation
• Interventions: Drug: Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.; Other: Patient-reported outcomes (PROs)

• Registration Number: NCT04151342
• Lead Sponsor: University Health Network, Toronto

Brief Summary

This study will collect data on Canadian cancer patients that have uncommon/rare changes in their tumours, such as alterations/rearrangements in the genetic material inside cells - known as deoxyribonucleic acid, or DNA, which acts as a map and gives directions to the cells on how to make other substances the body needs - because some of these changes have been found to respond to different drugs that help to stop the cancer. These rare changes occur in genes such as but not limited to ALK, EGFR, ROS1, BRAF, and NTRK which have targeted drugs in a family known as tyrosine kinase inhibitors (TKIs), and KRAS G12C mutation, which now has a targeted inhibitor drug therapy for patients with non small cell lung cancer (NSCLC). The goals for the study are to compare the natural history of such cancers and the treatment outcomes, including toxicities and patient-reported outcomes, for the different therapies.

Detailed Description

Molecular heterogeneity in cancer tumours make it a complex disease to manage and treat. However, there have been significant advancements made in the detection of molecular alterations and we are able to now define distinct disease subtypes which permit targeted selection of therapies, thus optimizing treatment responses for patients and improving their survival.

With CARMA-BROS we will address the objectives that follow.

Primary Objectives:

1. To create a cohort of patients through which to better understand the natural history of disease in Canadian cancer patients with tumours that have been molecularly subtyped and identified to have rare molecular alterations.

2. To compare the natural history, stage distribution, treatment outcomes such as treatment effectiveness (composite of disease progression or death) and treatment toxicities across different patients with different molecular alterations, receiving different lines and types of therapy.

Secondary Objectives:

3. To determine the incidence, time to development, prevalence, and outcomes of patients with specific patterns of spread, such as brain metastases compared to those without, by different therapies and by molecular alterations.

4. To better understand real-world treatment patterns of rare molecular alterations in the Canadian context, across geographic or other factors, and how treatment patterns evolve over time and as new therapies become available, how patients are investigated and how targeted and other biomarkers are used as part of clinical practice in these patients.

5. To assess quality of life in patients with rare molecular alterations across different stages, lines and types of therapy.

6. To perform exploratory health economic evaluations focused on the costs and benefits of managing patients with rare molecular alterations.

7. To perform biomarker analyses, where appropriate, to improve our understanding of these rare molecular alterations.

Study Timeline

• Study First Submitted: 2019-10-29
• Study First Submitted QC: 2019-11-01
• Study First Posted: 2019-11-05
• Study Start: 2020-01-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-30
• Last Update Posted: 2024-05-31
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• Patients ≥ 18 years at cancer diagnosis
• Diagnosed with malignant tumour(s) with molecular testing completed that identified rare molecular alterations
• Accessible/available molecular testing reports/documentation to confirm type(s) of molecular alteration(s) (resulting from the conduct of polymerase chain reaction [PCR] based next generation sequencing [NGS], immunohistochemistry [IHC], fluorescence in situ hybridization [FISH], liquid biopsy)
• Canadian resident received follow-up for cancer care in Canada or is currently receiving/planning follow-up for cancer care to occur in Canada at time of enrollment

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Exclusion Criteria

• Previous refusal of the deceased patient, when living, to enroll in this study or patient approached for this study is unable to provide informed consent

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Retrospective	Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.	Deceased cancer patients who had histologically confirmed rare molecular alterations in their tumours, such as in ALK, EGFR, ROS1, BRAF, and KRAS G12C from participating sites/cancer centres across Canada.
Prospective	Patient-reported outcomes (PROs)	Living cancer patients with histologically confirmed rare molecular alterations in their tumours, such as in ALK, EGFR, ROS1, BRAF, and KRAS G12C from participating sites/cancer centres across Canada.
Prospective	Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.	Living cancer patients with histologically confirmed rare molecular alterations in their tumours, such as in ALK, EGFR, ROS1, BRAF, and KRAS G12C from participating sites/cancer centres across Canada.

Primary Outcome Measures

Name	Time	Method
Composite of Progression Free Survival [PFS] or Overall Survival [OS]	From the start date of cancer therapy until the date of first documented progression or date of death (any cause), assessed up to 120 months	Composite of disease progression or death

Secondary Outcome Measures

Name	Time	Method
EORTC quality of life questionnaires (QLQ) - cancer patient-reported health related quality of life	Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)	Prospectively enrolled participants will complete the following health related quality of life surveys: EORTC QLQ-C30 (core) and EORTC QLQ-LC13 (disease specific module)
Brain metastasis/other metastatic tumours	From the start date of cancer therapy until the date of first documented brain/other metastasis, assessed up to 120 months	Confirmed through imaging (MRI, CT) or determined through treatment indication(s), for example, brain radiation therapy (surrogate for presence of brain metastasis)
EQ-5D-5L - patient-reported health related quality of life measure	Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)	Prospectively enrolled participants will complete the health related quality of life survey: EQ-5D-5L.
Patient-reported economic impact	Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)	Prospectively enrolled participants will complete the "Work Productivity and Activity Impairment Questionnaire: General Health" (WPAI:GH) and other economic impact questions that capture indirect costs incurred as a result of their disease.

Trial Locations

Locations (27)

William Osler Health System - Brampton Civic Hospital; 🇨🇦 Brampton, Ontario, Canada

Lawson Health Research Institute - London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

CancerCare Manitoba/University of Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Kingston Health Sciences Centre (KHSC); 🇨🇦 Kingston, Ontario, Canada

Cross Cancer Institute, University of Alberta - Alberta Health Services; 🇨🇦 Edmonton, Alberta, Canada

Tom Baker Cancer Centre - University of Calgary - Alberta Health Services; 🇨🇦 Calgary, Alberta, Canada

Princess Margaret Cancer Centre (PMCC) - University Health Network (UHN); 🇨🇦 Toronto, Ontario, Canada

Health Sciences North; 🇨🇦 Sudbury, Ontario, Canada

Hamilton Health Sciences - Juravinski Cancer Centre; 🇨🇦 Hamilton, Ontario, Canada

Centre hospitalier de l'Université de Montréal (CHUM); 🇨🇦 Montréal, Quebec, Canada

Jewish General Hospital; 🇨🇦 Montréal, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec; 🇨🇦 Québec City, Quebec, Canada

Saskatoon Cancer Centre; 🇨🇦 Saskatoon, Saskatchewan, Canada

Dr. H. Bliss Murphy Cancer Centre; 🇨🇦 Saint John's, Newfoundland and Labrador, Canada

Hôpital du Sacré-Coeur-de-Montréal (HSCM); 🇨🇦 Montréal, Quebec, Canada

St. Mary's Hospital Center; 🇨🇦 Montréal, Quebec, Canada

Queen Elizabeth II (QEII) Health Sciences Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Centre hospitalier universitaire de Sherbrooke (CHUS); 🇨🇦 Sherbrooke, Quebec, Canada

McGill University Health Centre; 🇨🇦 Montréal, Quebec, Canada

Dr. Everett Chalmers Regional Hospital; 🇨🇦 Fredericton, New Brunswick, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

Ottawa Hospital Cancer Centre; 🇨🇦 Ottawa, Ontario, Canada

Thunder Bay Regional Health Sciences Centre; 🇨🇦 Thunder Bay, Ontario, Canada

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

Sunnybrook Research Institute - Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Centre hospitalier de l'université de Québec - Université Laval; 🇨🇦 Québec City, Quebec, Canada

BC Cancer; 🇨🇦 Vancouver, British Columbia, Canada