Genomic Profiling in Cancer Patients

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT01775072

Collaborator

(none)

200

Enrollment

Locations

132

Duration (Months)

11.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Hematologic Cancers	Genetic: molecular profiling of tumors Genetic: Clinical Germline Analysis

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Genomic Profiling in Cancer Patients

Study Start Date :

Jan 1, 2013

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Pts with solid tumors Patients must have solid or hematologic cancer. for treatment on a . Patients must have undergone pathologic confirmation of their tumor at MSKCC and have either: 1) archival tissue available for analysis, 2) have fresh tissue collection planned as routine standard of care biopsy or part of a research biopsy under another clinical trial(or peripheral blood / bone marrow collection in the case of hematologic cancers) outside of the context of this protocol, or 3)archival tissue .available at an outside facility. For prospective genotyping tissue specimens from the primary site, a metastasis or recurrence will be used based upon the availability and quality of tissue.	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. Genetic: 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

Arm

Intervention/Treatment

Pts with solid tumors

Patients must have solid or hematologic cancer. for treatment on a . Patients must have undergone pathologic confirmation of their tumor at MSKCC and have either: 1) archival tissue available for analysis, 2) have fresh tissue collection planned as routine standard of care biopsy or part of a research biopsy under another clinical trial(or peripheral blood / bone marrow collection in the case of hematologic cancers) outside of the context of this protocol, or 3)archival tissue .available at an outside facility. For prospective genotyping tissue specimens from the primary site, a metastasis or recurrence will be used based upon the availability and quality of tissue.

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.

Genetic: 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

Outcome Measures

Primary Outcome Measures

frequency of "actionable" oncogenic mutations [1 year]
"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.

Secondary Outcome Measures

To determine the impact of molecular profiling results performed in the CLIA-setting on the treatment of patients. [1 year]
The Bioinformatics Core will assist in interpreting data generated by next-generation sequencing techniques such as WES and WGS.
interrogate the mechanisms [1 year]
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.
To explore the genetic mechanisms of tumorigenesis [2]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Part A:

Patients with a history of cancer or patients w ithout a documented cancer history undergoing a surgical procedure, biopsy, or liquid biopsy (for example cell free DNA testing) to confirm or exclude a cancer diagnosis.

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 and D:

Patients who have had an Allogenic bone marrow/stem cell transplant.
Patients with an acute or chronic myeloid neoplasm, histiocytic neoplasm, or other myeloproliferative disease (e.g. MDS, MPN, MDS/MPN) that would preclude the use of blood or saliva as a source of germline DNA. For example, patients with a hematologic malignancy with a high circulating disease burden (defined as >10% of WBCs from flow cytometry or CBC differential).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Vincent (Data Collection Only)	Bridgeport	Connecticut	United States	06606
2	Hartford Healthcare Cancer Institute @ Hartford Hospital	Hartford	Connecticut	United States	06102
3	Norwalk Hospital	Norwalk	Connecticut	United States	06850
4	Baptist Alliance MCI	Miami	Florida	United States	33143
5	Memoral Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
6	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
7	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
8	NYC Health & Hospitals /Lincoln Medical Center	Bronx	New York	United States	10451
9	Kings County Hopsital Center	Brooklyn	New York	United States	11203
10	Memorial Sloan Kettering Cancer Commack	Commack	New York	United States	11725
11	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
12	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
13	Metropolitan Hospital Center	New York	New York	United States	10029
14	Ralph Lauren Center for Cancer Care and Prevention	New York	New York	United States	10035
15	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
16	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
17	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103