Phil Stephens, PhD

Foundation Medicine Inc. (FMI) is interested in studying the concordance of genomic alterations between primary and/or metastatic surgical biopsies, and circulating tumor DNA (ctDNA) within different solid tumor types and has been developing an assay in order to do so.

The purpose of this study is to assess whether a new ctDNA assay developed by Foundation Medicine is able to detect genomic alterations in peripheral blood that are consistent with the genomic alterations detected in a patient's matched primary and/or metastatic tumor biopsy sample analyzed by the FoundationOne® test. Study sites will provide matched solid tumor and peripheral blood samples of cancer patients to FMI for the purpose of testing the concordance of the FMI ctDNA assay to the FoundationOne® test. Participation in this study is part of a broader 2000 patient study to determine which tumor types are most readily measured via ctDNA profiling, and to learn of the similarity between the alterations found in a patient's tumor biopsy and the ctDNA from their blood.

Concordance Between ctDNA Assay and FoundationOne

Study of Concordance Between Circulating Tumor DNA Assay and Foundation One Tissue Analysis For Genomic Alterations

Johns Hopkins University

Oncology Consultants

Comprehensive Blood and Cancer Center

Illinois CancerCare

Sanford Health

Eastchester Center for Cancer Care

Rutgers Cancer Institute of New Jersey

Cone Health

Nebraska Cancer Specialists

University of California, Davis

University of Chicago

Northeast Georgia Medical Center

Hematology Oncology Associates of Fredericksburg

Memorial Sloan Kettering Cancer Center

Oncology Hematology Care, Inc

Montefiore Medical Center

Quincy Medical Group

Prisma Health-Upstate

Mary Crowley Cancer Research Center

Texas Health

University of California, San Diego

Avera Cancer Institute

Foundation Medicine

Alteration of the genome under radiotherapy

genomic alterations

Maja Guberina, PD Dr. med. (MD), specialist

Ina Grübel

Maja Guberina, PD Dr. med. (MD)

The long-term goal is to define "signatures" in the form of genomic changes through sequence analyses of genomic DNA using modern Next Generation Sequencing (NGS) methods, which

1. determine the radiation exposure of humans.
2. provide information about the exposure (dose).
3. determine the radiation quality.
4. predict the repair capacity and radiation resistance of an individual.

The planned research work will investigate structural changes in DNA caused by loosely ionizing and high-LET (Linear Energy Transfer) radiation as well as their attribution to double-strand break repair pathways, which will be analysed in parallel using modern microscopy methods. Our aim is to incorporate sequencing technologies into the spectrum of methods used in radiation research and radiation protection. It is important for us to consider the practical requirements of radiation protection and to extend our experimental approaches to cell types relevant to radiation protection. For this reason, we have now created a separate work program that will focus specifically on sequence analyses in irradiated human lymphocytes. The aim is to successfully transfer the experimental approaches and bioinformatic analyses established in previous experiments in human skin fibroblasts to lymphocytes. Subjects can donate blood samples on a voluntary basis at predetermined times. Only subjects without previous radiotherapy, chemotherapy, immunotherapy, targeted therapy, etc. and without a previous tumor diagnosis in the medical history and in good performance status (ECOG 0-1) will be included.

Optimization of Radiation Protection Through Genomic Analyses

Optimization of Radiation Protection Through Genomic Analyses in the Analysis of Changes in Cells of the Hematopoietic System Before and During High Dose External Beam Radiotherapy

Radiotherapy of patients, quantitative tissue sampling, cell culture survival rate and mitotic index after predifined radiation treatment, Incidence of the sample and percentage

Radiation induced changes in the genome analyzing human skin fibroblasts and lymphocytes:

translocations that permitted cell division andm mismatch repair of radiation-induced DNA damage (PCR and M-FISH), Incidence of the sample and percentage

University Hospital, Essen

PD Dr. med. (MD) / specialist forradiation oncology, senior consultant

Neoplasms

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Neoplasm Metastasis

Hematologic Neoplasms

Hematologic Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Mitogens

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Serine

Threonine

Valine

all eligible patients entering the study will receive oral Vemurafenib as monotherapy.

Vemurafenib ZELBORAF 240 mg tablets Per OS 960 mg twice daily, to a total daily dose of 1,920 mg Cycles are defined in 28-day periods Disease response will be assessed every 8 weeks Safety will be assessed continuously

Treatment will be pursed until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient refusal.

Vemurafenib is a low molecular weight, orally available, inhibitor of BRAF serine-threonine kinase. Mutations in the BRAF gene which substitute the valine at amino acid position 600 result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation

Jean-Yves PI Blay, MD

Patients with metastatic or unresectable locally advanced malignancies harboring BRAF genomic alterations, the biological target of vemurafenib, and who are no more amenable to curative treatment.

To explore the efficacy of vemurafenib as a single agent across diverse type of tumors guided by the presence of identified activating molecular alterations in the vemurafenib target gene, per cohort.

This is a biology driven, trans-tumoral, multicentric phase II trial assessing the efficacy and the safety of the targeted agent vemurafenib as a monotherapy in cohorts of patients with identified activating molecular alterations in BRAF gene. A cohort is defined by a pathology and a BRAF- alteration (eg ovarian cancer with BRAF V600 mutation).

To explore the efficacy of vemurafenib per pathology and per target. To assess the safety profile of vemurafenib. To explore whether molecularly driven, high quality multi-tumor screening phase II trials are feasible in the French multiinstitutional, multidisciplinary setting.

To investigate the additional molecular mechanisms in patients with tumor response versus patients without tumor response within the same cohort.

The study will include 11 cohorts of adult patients with the following cancers and alterations:

* NSCLC V600 mutated
* Ovarian cancer V600 mutated
* Cholangiocarcinoma V600 mutated
* Thyroid cancer V600 mutated
* Prostatic cancer V600 mutated
* Bladder cancer V600 mutated
* Sarcoma/GIST V600 mutated
* Multiple myeloma V600 mutated
* Chronic Lymphocytic Leukemia (CLL) V600 mutated
* Hairy cell leukaemia (HCL) V600 mutated (this excludes Hairy Cell Leukemia variant types, marginal zone splenic lymphoma (MZL), splenic red pulp lymphoma (SRPL) patients)
* Other pathology / other alteration than those pre-defined above.

The cohort named "Other" will include adult patients with tumor harboring BRAF genomic alterations only tested via emerging biomarkers programs or molecular pangenomic programs:

* with any other non-predefined pathology harboring a V600 mutation
* Same or other non-predefined pathology harboring non V600 activating mutations
* Same or other non-predefined pathology harboring BRAF amplifications.

Phase 2 Study Assessing Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations

Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations

RECIST for solid tumors, International Myeloma Working Group Response Criteria for myeloma, IWCLL for CLL, clinical exam, blood tests (blood count) and bone marrow exam for Hairy Cell Leukemia.

The assessment of safety will be based mainly on the frequency of adverse events coded using the common toxicity criteria (CTC-V4.0) grade.

National Cancer Institute, France

Fondation ARC

Hoffmann-La Roche

UNICANCER

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Concordance Between ctDNA Assay and FoundationOne	NCT02620527	Circulating Tum... Cancer Neoplasms Genomic Testing Genomic Alterat...		18 Years -	Foundation Medicine
Optimization of Radiation Protection Through Genomic Analyses	NCT06253338	DNA Cancer Radiation	genomic alterat...	18 Years -	University Hospital, Essen
Optimization of Radiation Protection Through Genomic Analyses	NCT06253338	DNA Cancer Radiation	genomic alterat...	18 Years -	University Hospital, Essen
Phase 2 Study Assessing Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations	NCT02304809	Solid Tumors Hematologic Can... Metastatic Canc...	Vemurafenib	18 Years -	UNICANCER
Optimization of Radiation Protection Through Genomic Analyses	NCT06253338	DNA Cancer Radiation	genomic alterat...	18 Years -	University Hospital, Essen

Spots Global Cancer Trial Database for genomic alterations