Clinical trial NCT04151342: CAnadian CAncers With Rare Molecular Alterations (CARMA) - Basket Real-world Observational Study (BROS)
Official title: CAnadian CAncers With Rare Molecular Alterations (CARMA) - Basket Real-world Observational Study (BROS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Keywords: observational study
cancer
cancer therapies
molecular alterations
real-world evidence
real-world data
tyrosine kinase inhibitors
ambispective
ras GTPase inhibitors
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Takeda Canada, Inc.
name: Applied Health Research Centre
name: Programs for Assessment of Technology in Health Research Institute
name: AstraZeneca
name: Amgen
name: Bayer
name: AnHeart Therapeutics Inc.
First posted: 2019-11-05
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer patients living and deceased who have/had a histologically confirmed rare molecular alteration in their tumours, such as but not limited to ALK, EGFR, ROS1, BRAF, and KRAS G12C from participating sites/cancer centres across Canada.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite of Progression Free Survival [PFS] or Overall Survival [OS]
timeFrame: 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 outcomes:
measure: Brain metastasis/other metastatic tumours
timeFrame: From the start date of cancer therapy until the date of first documented brain/other metastasis, assessed up to 120 months
measure: EORTC quality of life questionnaires (QLQ) - cancer patient-reported health related quality of life
timeFrame: Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)
measure: EQ-5D-5L - patient-reported health related quality of life measure
timeFrame: Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)
measure: Patient-reported economic impact
timeFrame: Baseline and serial changes every 3 months, including whenever there is a change in treatment, up to 120 months (the duration of this study)
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - University of Calgary - Alberta Health Services
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute, University of Alberta - Alberta Health Services
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba/University of Manitoba
state: Manitoba
city: Fredericton
country: Canada
facility: Dr. Everett Chalmers Regional Hospital
state: New Brunswick
city: Saint John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Queen Elizabeth II (QEII) Health Sciences Centre
state: Nova Scotia
city: Brampton
country: Canada
facility: William Osler Health System - Brampton Civic Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre (KHSC)
state: Ontario
city: London
country: Canada
facility: Lawson Health Research Institute - London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Centre
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre (PMCC) - University Health Network (UHN)
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute - Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur-de-Montréal (HSCM)
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montréal
country: Canada
facility: St. Mary's Hospital Center
state: Quebec
city: Québec City
country: Canada
facility: Centre hospitalier de l'université de Québec - Université Laval
state: Quebec
city: Québec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke (CHUS)
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Geoffrey Liu, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: