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

Cancer Clinical Trial

— CARMA-BROS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04151342
• Other study ID #: CARMA-BROS
• Secondary ID: 18-59021632
• Status: Recruiting
• Start date: January 17, 2020
• Est. completion date: December 2025

Study information

• Verified date: October 2023
• Source: University Health Network, Toronto
• Contact: Roula Raptis, MSc
• Phone: 416-864-6060
• Email: Roula.Raptis[@]unityhealth.to
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Cancer
• Cancer, Therapy-Related
• Gene Fusion
• Genetic Alteration
• Malignancies Multiple
• Malignant Solid Tumor
• Molecular Sequence Variation
• Neoplasms, Second Primary
• Receptor Tyrosine Kinase Gene Mutation
• RTK Family Gene Mutation

Intervention

Drug:
• Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.
Observing cancer patients who have received or are currently receiving tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapies for their cancer treatment.

Other:
• Patient-reported outcomes (PROs)
Prospectively enrolled participants will be provided with survey packets comprised of different PRO instruments at the initial/baseline visit, at 3 month follow up intervals and at the time when treatment/therapy is changed.

Locations

Country	Name	City	State
Canada	William Osler Health System - Brampton Civic Hospital	Brampton	Ontario
Canada	Tom Baker Cancer Centre - University of Calgary - Alberta Health Services	Calgary	Alberta
Canada	Cross Cancer Institute, University of Alberta - Alberta Health Services	Edmonton	Alberta
Canada	Dr. Everett Chalmers Regional Hospital	Fredericton	New Brunswick
Canada	Queen Elizabeth II (QEII) Health Sciences Centre	Halifax	Nova Scotia
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	Kingston Health Sciences Centre (KHSC)	Kingston	Ontario
Canada	Lawson Health Research Institute - London Health Sciences Centre	London	Ontario
Canada	Centre hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec
Canada	Hôpital du Sacré-Coeur-de-Montréal (HSCM)	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	St. Mary's Hospital	Montréal	Quebec
Canada	Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec	Québec City	Quebec
Canada	Centre hospitalier universitaire de Sherbrooke (CHUS)	Sherbrooke	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Princess Margaret Cancer Centre (PMCC) - University Health Network (UHN)	Toronto	Ontario
Canada	Sunnybrook Research Institute - Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	CancerCare Manitoba/University of Manitoba	Winnipeg	Manitoba

Sponsors (7)

Lead Sponsor	Collaborator
University Health Network, Toronto	Amgen, Applied Health Research Centre, AstraZeneca, Bayer, Programs for Assessment of Technology in Health Research Institute, Takeda Canada, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Progression Free Survival [PFS] or Overall Survival [OS]	Composite of disease progression or death	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
Secondary	Brain metastasis/other metastatic tumours	Confirmed through imaging (MRI, CT) or determined through treatment indication(s), for example, brain radiation therapy (surrogate for presence of brain metastasis)	From the start date of cancer therapy until the date of first documented brain/other metastasis, assessed up to 120 months
Secondary	EORTC quality of life questionnaires (QLQ) - cancer patient-reported health related quality of life	Prospectively enrolled participants will complete the following health related quality of life surveys: EORTC QLQ-C30 (core) and EORTC QLQ-LC13 (disease specific module)	Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)
Secondary	EQ-5D-5L - patient-reported health related quality of life measure	Prospectively enrolled participants will complete the health related quality of life survey: EQ-5D-5L.	Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)
Secondary	Patient-reported economic impact	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.	Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)