Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Antibodies

Antibodies, Monoclonal

Bevacizumab

Cetuximab

Leucovorin

Levoleucovorin

Oxaliplatin

Folic Acid

Immunoglobulins

Panitumumab

Antineoplastic Agents, Immunological

Folinic Acid

Folate

Vitamin B9

All patients will recieve chemotherapy FOLFOX (oxaliplatin 85 mg/m2 + folinic acid 400 mg/m2 + FU 400 mg/m2 bolus and FU 2400 mg/m2 46-hour insusion q2w) + anti-EGFR monoclonal antibody (cetuximab 500 mg/m2 q2w or panitumumab 6 mg/kg q2w) until disease progression or unacceptable toxicity. It is permited to withdraw oxaliplatin after 8 cycles.

All patients will recieve chemotherapy FOLFOX (oxaliplatin 85 mg/m2 + folinic acid 400 mg/m2 + FU 400 mg/m2 bolus and FU 2400mg/m2 46-hour insusion q2w). Monoclonal antibody will be added to chemotherapy after 1-2 cycles based on molecular profile results: anti-EGFR (cetuximab 500 mg/m2 q2w or panitumumab 6 mg/kg q2w) for hyperselected wild type tumors or bevacizumab 5 mg/m2 q2w for mutant profile.

Patients will recieve therapy until disease progression or unacceptable toxicity. It is permited to withdraw oxaliplatin after 8 cycles.

FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles

Ilya Pokataev, phD

Maria Byakhova, phD

Mikhail Fedianin, phD

Alexey Tryakin, phD

Mikhail Byakhov, PhD

Patients meeting the inclusion criteria will be randomized 1:1 into Cohort A (n ≈ 177) or Cohort BC (n ≈ 177). Cohort A is the control: patients receive combination chemotherapy with FOLFOX plus anti-EGFR therapy (panitumumab or cetuximab) based on RAS/BRAF wild-type data, according to clinical guidelines.

The BC cohort begins FOLFOX chemotherapy and simultaneously undergoes extensive molecular genetic profiling. Further, the BC cohort, depending on the profile, is divided into cohort B - patients without changes in alternative oncogenes, and cohort C - with changes in alternative oncogenes. The expected cohort ratio is 3:1 (\~120 and \~40 patients). Cohort B begins to receive anti-EGFR therapy in addition to chemotherapy, and the potentially resistant cohort C continues to receive chemotherapy alone or begins to receive bevacizumab if there are no contraindications.

In total, the study plans to include 355 patients diagnosed with unresectable metastatic colorectal cancer with a left-sided localization of the primary tumor, who have not previously received systemic therapy for metastatic disease, have wild-type KRAS/NRAS/BRAF, or have wild-type KRAS/NRAS with unknown BRAF status in no contraindications to targeted therapy (cetuximab/panitumumab/bevacizumab).

Patients meeting the inclusion criteria will be randomized 1:1 into Cohort A (n ≈ 177) or Cohort BC (n ≈ 177). Cohort A is the control: patients receive combination chemotherapy with FOLFOX plus anti-EGFR therapy (panitumumab or cetuximab) based on RAS/BRAF wild-type data, according to clinical guidelines. Next, this cohort, after completion of the protocol, undergoes extended profiling, according to the results of which it is divided into cohorts A1 and A2. Cohort A1 includes patients without changes in alternative oncogenes (N ≈ 120), cohort A2 includes patients with changes (N ≈ 40).

The BC cohort begins FOLFOX chemotherapy and simultaneously undergoes extensive molecular genetic profiling. Further, the BC cohort, depending on the profile, is divided into cohort B - patients without changes in alternative oncogenes, and cohort C - with changes in alternative oncogenes. The expected cohort ratio is 3:1 (\~120 and \~40 patients). Cohort B begins to receive anti-EGFR therapy in addition to chemotherapy, and the potentially resistant cohort C continues to receive chemotherapy alone or begins to receive bevacizumab if there are no contraindications.

randomize and compare contol and experimental groups

Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer

Predictive Value of Other Oncogene Mutations for Anti-EGFR Monoclonal Antibodies Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer: Multicenter Randomized Phase III Trial

Intention to treat, Calculated from start of therapy to date of disease progression or death

Calculated from start of therapy to date of last contact or death

Atlas Biomed

N.N. Blokhin National Medical Research Center of Oncology

Moscow MultidisciplinaryClinical Center Kommunarka

City Clinical Oncology Hospital No 1

Head of department of medical oncology

Neoplasms, Second Primary

Amino Acids

Immunomodulating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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.

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.

Observing cancer patients who have received or are currently receiving tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapies for their cancer treatment.

Cancer treatment with tyrosine kinase inhibitors (TKIs) or other molecularly targeted therapeutic agents.

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.

Patient-reported outcomes (PROs)

Roula Raptis, MSc

Geoffrey Liu, MD, MSc

Vishal Navani, MA (Oxon), MBBS, MRCP, FRACP

Quincy Siu-Chung Chu, MD, FRCPC

Cheryl Ho, MD, FRCPC

Shantanu Banerji, MD, FRCPC

Luisa Galvis-Gomez, MD

Elizabeth Faour, MD

Stephanie Snow, MD, FRCPC

Parneet Cheema, MD, FRCPC

Rosalyn Juergens, MD, PhD

Sofia Genta, MD

Sara Kuruvilla, MD, FRCPC

Paul Wheatley-Price, MBChB, FRCP(UK), MD

Abhenil Mittal, MD

Olexiy Aseyev, MD

Devalben Patel, BSc, MLT

Ronald Burkes, MD, FRCPC

Ines Menjak, MD, FRCPC

Normand Blais, MD, MSc

Kevin Jao, MD, PhD

Jason Agulnik, MD

Jonathan Spicer, MD, PhD

Nicholas Meti, MD

Nicolas Marcoux, MD, FRCPC

Philippe Joubert, MD, PhD

Nicole Bouchard, MD

Ayesha Bashir, MD, FRCPC

Sunil Yadav, MD

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.

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.

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

Composite of disease progression or death

Confirmed through imaging (MRI, CT) or determined through treatment indication(s), for example, brain radiation therapy (surrogate for presence of brain metastasis)

Prospectively enrolled participants will complete the following health related quality of life surveys: EORTC QLQ-C30 (core) and EORTC QLQ-LC13 (disease specific module)

Prospectively enrolled participants will complete the health related quality of life survey: EQ-5D-5L.

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.

Takeda Canada, Inc.

Applied Health Research Centre

Programs for Assessment of Technology in Health Research Institute

AstraZeneca

Amgen

Bayer

AnHeart Therapeutics Inc.

University Health Network, Toronto

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Patients with newly diagnosed glioma that receive tumor resection

Glioma groups based on molecular pathology or genetic variation

Zhenyu Zhang, Dr.

This study aims to collect clinical, radiological, pathological, molecular and genetic data including detailed clinical parameters, MR and histopathology images, molecular pathology and genetic data. This study seeks to find the prognostic and clinical significance based on molecular and genetic biomarkers/subgroups of gliomas.

Precise classification based on molecular and genetic biomarkers/subgroups for gliomas is challenging. This study aims to collect clinical, radiological, pathological, molecular and genetic data including detailed clinical parameters, MR and histopathology images, molecular pathology (1p/19q co-deletion, MGMT methylation, IDH and TERTp mutations, etc) and genetic data (Whole exome sequencing, RNA sequencing, proteomics, etc). This study seeks to find the prognostic and clinical significance based on molecular and genetic biomarkers/subgroups of gliomas.

All participants have signed the informed consent. Fresh frozen tissues of participants are collected immediately after tumor resection and preserved in liquid nitrogen. Whole exome sequencing, RNA sequencing and proteomics are planed to be conducted.

Survival Significance of Molecular Pathology and Genetic Variation in Brain Gliomas

Survival Significance and Clinical Characteristics of Molecular Pathology and Genetic Variation in Brain Gliomas

The length of time from enrollment until the time of death (OS, overall survival)

The First Affiliated Hospital of Zhengzhou University

Doctor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer	NCT06226857	Colorectal Neop... Chemotherapy Ef... Molecular Seque...	Cetuximab	18 Years - 99 Years	City Clinical Oncology Hospital No 1
CAnadian CAncers With Rare Molecular Alterations (CARMA) - Basket Real-world Observational Study (BROS)	NCT04151342	Cancer Malignancies Mu... Malignant Solid... Cancer, Therapy... Molecular Seque... Genetic Alterat... Gene Fusion Receptor Tyrosi... RTK Family Gene... Ras (Kras or Nr...	Cancer treatmen... Patient-reporte...	18 Years -	University Health Network, Toronto
Survival Significance of Molecular Pathology and Genetic Variation in Brain Gliomas	NCT04216537	Glioma Molecular Seque... Genetic Change	Glioma groups b...	1 Year - 95 Years	The First Affiliated Hospital of Zhengzhou University
Survival Significance of Molecular Pathology and Genetic Variation in Brain Gliomas	NCT04216537	Glioma Molecular Seque... Genetic Change	Glioma groups b...	1 Year - 95 Years	The First Affiliated Hospital of Zhengzhou University

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