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

Study Overview
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Brief Summary
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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
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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: 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. 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: 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. 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. To assess quality of life in patients with rare molecular alterations across different stages, lines and types of therapy. To perform exploratory health economic evaluations focused on the costs and benefits of managing patients with rare molecular alterations. To perform biomarker analyses, where appropriate, to improve our understanding of these rare molecular alterations.

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

Conditions
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Cancer, Malignancies Multiple, Malignant Solid Tumor, Cancer, Therapy-Related, Molecular Sequence Variation, Genetic Alteration, Gene Fusion, Receptor Tyrosine Kinase Gene Mutation, RTK Family Gene Mutation, Ras (Kras or Nras) Gene Mutation

Intervention / Treatment
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* Drug: Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.
* Other: Patient-reported outcomes (PROs)


Participation Criteria
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Eligibility Criteria
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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

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective<br>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. | Drug: Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.<br>* Observing cancer patients who have received or are currently receiving tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapies for their cancer treatment.<br>Other: Patient-reported outcomes (PROs)<br>* 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.<br>|
| Retrospective<br>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. | Drug: Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.<br>* Observing cancer patients who have received or are currently receiving tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapies for their cancer treatment.<br>|
| Comparator group<br>All cancer patients without rare molecular alterations in their tumours. This group will be established in order to determine baseline characteristics and outcomes, including treatment outcomes, of more standard treatments such as systemic chemotherapy or immunotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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observational study, cancer, cancer therapies, molecular alterations, real-world evidence, real-world data, tyrosine kinase inhibitors, ambispective, ras GTPase inhibitors