Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Sarcoma

Thoracic Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Osimertinib

Mitogens

Sotorasib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

ERAS-007 will be orally administered in combination with osimertinib to study participants with EGFRm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

ERAS-007 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

ERAS-601 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

ERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with osimertinib to study participants with EGFRm NSCLC.

ERAS-007 will be orally administered at the recommended dose (as determined from Part 2) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.

ERAS-601 will be orally administered at the recommended dose (as determined from Part 3) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.

ERAS-007

ERAS-601

Joyce Antal

* To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced non-small cell lung cancer (NSCLC).
* To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies.
* To evaluate the antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies.
* To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.

This is a Phase 1b, open-label, multicenter master protocol evaluating safety, tolerability, and antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced NSCLC. The study will commence with the following dose escalation cohorts: ERAS-007 plus osimertinib in study participants with advanced NSCLC harboring epidermal growth factor receptor-sensitizing mutation(s) (EGFRm); ERAS-007 or ERAS-601 plus sotorasib in study participants with advanced NSCLC harboring Kirsten rat sarcoma G12C mutation (KRAS G12Cm). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with advanced EGFRm or KRAS G12Cm NSCLC.

A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC

A Phase 1b Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Non-Small-Cell Lung Cancer

Incidence and severity of treatment-emergent AEs and serious AEs

Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies

Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies

Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies

Half-life of ERAS-007 or ERAS-601 and other cancer therapies

Based on assessment of radiographic imaging per RECIST version 1.1

Erasca, Inc.

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Philippe CASSIER

Philippe CASSIER, MD

PATAKESS is a monocentric non interventional cohort study (prospective (alive patients) and retrospective (dead patients with biological material from surgery and/or biopsies already collected)).

PATAKESS consists of clinical and biological analyses of exocrine pancreatic tumors. Data are derived from tumor samples taken for routine health care purposes in patients managed at Centre Léon Bérard (Lyon-France) since January 2010. The main objective is to determine correlation between biological and clinical characterizations of patients suffering from exocrine pancreatic tumor.

Pancreatic adenocarcinoma cancer is an aggressive cancer which represents 95% of pancreatic cancer. Pancreatic adenocarcinoma cancer is one of the deadliest cancers (5th cause of death per cancer) ; it has a very poor prognosis: 5-year survival (regardless of all stades at diagnosis). Pancreatic adenocarcinoma cancer is characterized by early metastasis. Therefore, development of efficient systemic therapeutics is one of the keys to improving prognosis. Newly developed immune check-point inhibitors seem to have limited efficacy in pancreatic adenocarcinoma except for MSI-H (Microsatellite instability-high) or dMMR (mismatch repair deficient)/MSI-H tumors.

However, recent data suggest that immune surveillance could control metastatic dissemination of pancreatic adenocarcinoma cancer. Several studies showed strong interactions between pancreatic tumor cells and tumor stroma in metastatic dissemination and in resistance to conventional therapeutics. Many data about pancreatic primitive tumors from murine animals models are available ; however few data on tumor stroma and its interactions with tumor cells of metastasis from adenocarcinoma pancreas are available. Few data on correlation between molecular alterations types (mutations, deletions, amplifications) in pancreatic adenocarcinoma cells and tumor stroma characteristics (primitive and metastatic stroma (cells composition, immune infiltration)) are also available.

In PATAKESS study, clinical and biological data are derived from tumor samples taken for routine health care purposes in patients managed at Centre Léon Bérard (Lyon-France) since January 2010.

Exocrine pancreatic tumor samples (from initial diagnosis biopsy and/or from surgery specimen of primitive tumor and/or from metastases) and blood sample (collected during a routine check-up)

PATAKESS Protocol : Clinical and Biological Analysis of Exocrine Pancreatic Tumors

Clinical characteristics of patients are consistent with tumor response at each treatment line and disease stage at diagnosis ; Biological characteristics will describe molecular alterations of the tumor by sequencing techniques like Next Generation Sequencing (NGS)

Comparative characterization of the different stroma by immunological detection

Comparative characterization of the different stroma by NGS

Centre Leon Berard

Neoplasms, Second Primary

Immunomodulating 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.

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

Stomach Neoplasms

Stomach Diseases

Stomach Cancer

Patients with confirmation of, or suspicion of, a heritable gastric malignancy disorder

Cathleen E Hannah, C.R.N.P.

Jeremy L Davis, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

Certain stomach cancers are rare, but they have high mortality rates. Researchers want to learn more about gastric (stomach) tumors. In this study, they want to collect data from people who have stomach cancer or are at risk to get it. This data will be used to see if the people can be in other studies.

Objective:

To study tissue from stomach tumors and find people eligible for more studies on gastric cancer.

Eligibility:

Age greater than or equal to 2 years old who have or may have stomach cancer, lesions that may be related to stomach cancer, or an inherited disorder that leads to stomach cancer.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Heart tests

Scans or ultrasound.

For the scans, participants lie in a machine that takes pictures. For some scans, they will swallow or be injected with a small amount of radioactive material. Special cameras will show the material in the body.

Tumor sample taken with a needle or surgery

Some participants will have an endoscopy. A long, flexible tube with a camera will be inserted through the mouth into the stomach. The tube will collect tissue from the stomach.

Some participants may have follow-up visits. Some may be invited to join other studies. Others will be contacted by phone to see how they are doing.

...

Background:

* Greater than 90% of gastric tumors are of epithelial origin and are classified as adenocarcinomas; the remainders include GIST, carcinoid and lymphoma
* Gastric adenocarcinoma is rare in the United States (incidence 7.4 per 100,000)
* Mortality rates are high with an estimated 5-year overall survival of 25% - 30%
* Up to 3% of gastric adenocarcinomas occur as part of a heritable cancer syndrome
* Molecular sub-classification of gastric adenocarcinomas has been reported, however translation of these findings into clinical management of patients has yet to occur

Objectives:

* To permit clinical and laboratory evaluation and molecular profiling of tumor tissue from patients with gastric malignancies or non-invasive (neoplastic) conditions
* Assess eligibility for enrollment in studies of gastric cancer conducted in the CCR
* To allow long-term follow up of patients with gastric tumors, or heritable gastric malignancy syndromes, to support clinical and preclinical research particularly related to molecular alterations in gastric tumors and their response to therapy

Eligibility:

Patients with the following are eligible:

* Malignant or non-invasive, neoplastic lesions of the stomach confirmed by histopathology or cytopathology;
* Suspicious lesion not yet confirmed, but considered likely related to the stomach pending further evaluation;
* Confirmed, deleterious germline mutation (including but not limited to HDGC, GAPPS) known to predispose to gastric tumors;
* Confirmed or suspicious heritable gastric malignancy disorder;
* Clinically suspicious personal or family medical history of gastric cancer or gastric cancer syndrome that warrants genetics evaluation.
* Age greater than or equal to 2 years.

Design:

* This protocol is designed to facilitate clinical evaluation, molecular tumor profiling, and long-term follow up of patients with gastric tumors
* Patients will be screened and clinical evaluation performed to determine eligibility for other CCR trials for gastric tumors
* No investigational treatment will be administered and no procedures will be done for only research purposes on this protocol.
* It is anticipated that the protocol will enroll a maximum of 250 patients.

Prospective Evaluation and Molecular Profiling in People With Gastric Tumors

Prospective Evaluation and Molecular Profiling in Patients With Gastric Tumors

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

long-term follow up of patients with gastric tumors, or heritable gastric malignancy syndromes screened on this study, to support clinical and preclinical research particularly related to molecular alterations in gastric tumors and their response to therapy

determination of eligibility for enrollment in studies of gastric cancer conducted in the CCR

Tissue samples collected to permit clinical and laboratory evaluation and molecular profiling of tumor tissue from patients with gastric malignancies or non-invasive (neoplastic) conditions

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC	NCT04959981	Advanced Non-sq...	ERAS-007 ERAS-601 Osimertinib Sotorasib	18 Years - 99 Years	Erasca, Inc.
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC	NCT04959981	Advanced Non-sq...	ERAS-007 ERAS-601 Osimertinib Sotorasib	18 Years - 99 Years	Erasca, Inc.
PATAKESS Protocol : Clinical and Biological Analysis of Exocrine Pancreatic Tumors	NCT04011982	Exocrine Pancre...		18 Years -	Centre Leon Berard
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
Prospective Evaluation and Molecular Profiling in People With Gastric Tumors	NCT03027427	Stomach Neoplas... Stomach Cancer		2 Years -	National Institutes of Health Clinical Center (CC)
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC	NCT04959981	Advanced Non-sq...	ERAS-007 ERAS-601 Osimertinib Sotorasib	18 Years - 99 Years	Erasca, Inc.

Spots Global Cancer Trial Database for molecular alterations