Genomic Profiling in Cancer Patients

Solid Tumors Clinical Trial

Official title:

Genomic Profiling in Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01775072
• Other study ID #: 12-245
• Status: Recruiting
• Start date: January 2013
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: David Solit, MD
• Phone: 646-888-2641
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to determine whether certain genes in cancer may be abnormal. When a gene is abnormal this is called a mutation. Most mutations in cancer cells are not inherited (passed down from parents) but happen after birth in the cancer itself. Most cancers have many mutations. Some of these mutations are important for the cancer cells to survive while others are not. The goal of this study is test cancer for certain mutations using leftover tumor tissue from a previous surgery or biopsy. Participants will also be asked to provide a tube of blood cheek (also known as a buccal) swab, or a saliva sample that contains normal genes for comparison. The purpose of Part B of this study is to: Understand how genetic changes in tumor effect the chance of responding to experimental cancer treatment. Understand how the genes in the tumor change overtime in response to targeted cancer treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Part A:

• Patients with a history of cancer or patients without a documented cancer history undergoing a surgical procedure, endoscopy, biopsy, or liquid biopsy (for example cell free DNA testing) to confirm or exclude a cancer diagnosis, or
• Any participant having a test or procedure that has the potential to provide a specimen that can be banked for future research purposes, or
• Any participant who has already had a diagnostic or therapeutic procedure that has yielded tissue, blood or other bodily fluids presently in the archive but who has not yet been approached to participate is also eligible.

Part B:

• Patients must be successfully registered to Part A of MSKCC IRB# 12-245
• Prior written approval for patient consent obtained from the Principal/Co-Principal Investigator of MSKCC IRB # 12-245.

Part C:

• Patient must be receiving ongoing care at MSK or a CHERPn/ Alliance/Affiliate site or have previously consulted with an MSK physician.
• Patient must have successfully consented to Part A of this study.

Part D:

• Patients with no personal cancer history at increased risk for cancer development due to family history, molecular cancer marker, know carrier status of a gene associated with increased cancer risk or prior/ongoing environmental exposures or lifestyle factors. Exclusion Criteria:

All Parts:

• Unwilling or unable to provide informed consent.

Part C:

• All patients consenting to Part A are eligible to consent to 12-245, Part C. Most patients will be eligible to receive clinical germline testing with return of results to the patient/health care providers. However, several exclusion criteria apply and are outlined below

1. Solid tumor patients: Secondary germline analysis using BAM files generated for MSK-IMPACT testing is not an option for patients with solid tumors and an acute or chronic hematologic neoplasm that would preclude the use of blood or saliva as a source of germline DNA. Such patient may be eligible for primary germline testing using a non-blood source of germline DNA as per standard clinical guidelines. Solid tumor patients who have had an allogenic bone marrow/stem cell transplant will only be considered eligible for germline testing under Part C if a sample adequate for germline testing had previously been collected prior to allogenic bone marrow/stem cell transplant.

2. Hematologic cancer patients: For patients with a hematopoietic neoplasm, germline testing may be an option under Part C using nail clippings or another non-blood source of DNA as per standard clinical practice. For patients who have had an allogenic bone marrow/stem cell transplant, clinical germline testing will only be considered under Part C if a sample adequate for germline testing had previously been collected prior to Allogenic bone marrow/stem cell transplant. Part D

• Exclusion criteria are same as those for Part C outlined above.

Related Conditions & MeSH terms

• Hematologic Cancers
• Hematologic Neoplasms
• Solid Tumors

Intervention

Genetic:
• molecular profiling of tumors
Part A is the molecular profiling of tumors. No new tumor biopsies will be performed in the context of Part A. If a pt does have a surgery or tumor biopsy , leftover tissue (or an additional core) from this procedure may be used for molecular profiling. Clinical Assay(s): This testing will be performed in the CLIA-certified Molecular Diagnostics Service laboratory. Research Assay(s): This protocol will also be used as a platform to pilot the use of investigational "next-generation" profiling technologies .including whole exome sequencing, whole genome sequencing RNA sequencing cell-free tumor DNA/RNA sequencing, proteomics, & others. To confirm the findings obtained on these assays using an orthogonal assay, additional sequencing such as Sanger,Sequenom, MiSeq or IMPACT testing may be utilized in either the CLIA or non-CLIA setting Part B: DTC Cohort Pts successfully registered to Part B of this study will be eligible for minimal risk collection & research biopsies.
• Clinical Germline Analysis
Part C: Clinical Germline Analysis Participants who have donated a matched normal peripheral blood sample for comparison to somatic sequence will be offered the opportunity to have that germline DNA sample analyzed for the presence of deleterious or likely deleterious mutations in genes on the MSK-IMPACT panel that are known to be linked to inherited susceptibility or that are included on consensus lists of genes that should undergo secondary analysis (e.g. the "ACMG list"). Part D: Germline Profiling for Individuals at Elevated Cancer Risk

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	St. Vincent (Data Collection Only)	Bridgeport	Connecticut
United States	New York Cancer & Blood Specialists (Data collection only)	Bronx	New York
United States	NYC Health & Hospitals /Lincoln Medical Center	Bronx	New York
United States	Kings County Hopsital Center	Brooklyn	New York
United States	Memorial Sloan Kettering Cancer Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Healthcare Cancer Institute @ Hartford Hospital	Hartford	Connecticut
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	Baptist Alliance MCI	Miami	Florida
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Metropolitan Hospital Center	New York	New York
United States	Ralph Lauren Center for Cancer Care and Prevention	New York	New York
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	frequency of "actionable" oncogenic mutations	"Actionable" mutations will be defined as either 1) a mutation shown to predict for sensitivity or resistance to a drug FDA approved for use in another cancer indication or 2) a mutation which predicts for sensitivity or resistance in preclinical models to an investigational class of drugs.	1 year
Secondary	To determine the impact of molecular profiling results performed in the CLIA-setting on the treatment of patients.	The Bioinformatics Core will assist in interpreting data generated by next-generation sequencing techniques such as WES and WGS.	1 year
Secondary	interrogate the mechanisms	underlying response and resistance (de-novo and acquired) to targeted therapy. The research assay(s) used to accomplish this will vary based on the clinical setting and tissue available and may include Sanger, Sequenom, MiSeq, exon-capture (ie: IMPACT), whole exome, and whole genome sequencing.	1 year
Secondary	To explore the genetic mechanisms of tumorigenesis	in a subset of specimens with no identifiable culpritic genomic alterations on highly-multiplexed next-generation sequencing (i.e.: IMPACT testing) by using even more comprehensive investigational profiling techniques such as whole exome sequencing, whole genome sequencing or RNA sequencing	2

External Links

•   Memorial Sloan Kettering Cancer Center