Molecular Profiling in Tissue Samples From Patients With Cancer Who Are Exceptional Responders to Treatment

NCT02243592 | Active Not Recruiting DMC

• 3 other identifiers: NCI-2014-015859671UM1CA186704
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 73

Brief Summary

This pilot research trial studies molecular profiling in tissue samples from patients with cancer who got better with treatment that didn't work for most other patients with the same disease. Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to how well patients respond to treatment.

Conditions

Malignant Neoplasm

Outcome Measures

Primary Outcomes (9)

• Molecular features in tissue samples from patients who were exceptional responders

  The molecular features of the tumors in the patients will be discernible as distinct to the tumor by comparison to (i) samples from normal tissue in the same patient and (ii) databases of similar data for normal and other tumor types.

  Baseline

• Putative mechanisms of action of the treatments that the patients received when they experienced their exceptional responses

  The associations between identified molecular features and the putative mechanisms of action of the treatments that the patients received when they experienced their exceptional responses will be explored. Statistical analyses will be primarily descriptive.

  Baseline

• Number of cases identified as potential exceptional responders

  Statistical analyses will be primarily descriptive.

  Baseline

• Percentage of identified potential cases confirmed to be exceptional responders

  Statistical analyses will be primarily descriptive.

  Baseline

• Percentage of confirmed exceptional responders for which adequate tissue with appropriate informed consent is acquired

  Statistical analyses will be primarily descriptive.

  Baseline

• Percentage of acquired cases with tissue for which at least the minimum molecular characterization is successfully obtained

  Statistical analyses will be primarily descriptive.

  Baseline

• Percentage of molecularly characterized cases for which a Molecular Characterization report identified (without reference to the drug received by the patient) at least one feature judged to have potential therapeutic relevance

  Promising discoveries will be summarized for the group of cases for which the minimum molecular characterization was successfully obtained. For each such case, molecular data will be reviewed by an expert panel ("Panel") to identify interesting features. All estimated proportions will be accompanied by exact 95% confidence intervals.

  Baseline

• Percentage of cases with >= 1 feature on Molecular Characterization report that was judged to have potential therapeutic relevance to the specific class of drug the patient actually received when the exceptional response was experienced

  Promising discoveries will be summarized for the group of cases for which the minimum molecular characterization was successfully obtained. For each such case, molecular data will be reviewed by the Panel to identify interesting features. All estimated proportions will be accompanied by exact 95% confidence intervals.

  Baseline

• Percentage of cases with >= 1 feature that correlates with the mechanism of action of the specific grant to which the exceptional response occurred that was found after further analyzing the molecular profile data for relevant molecular abnormalities

  Promising discoveries will be summarized for the group of cases for which the minimum molecular characterization was successfully obtained. For each such case, molecular data will be reviewed by the Panel to identify interesting features. All estimated proportions will be accompanied by exact 95% confidence intervals.

  Baseline

Study Arms (1)

Ancillary-Correlative (molecular profiling)

Previously collected tissue samples are analyzed via whole exome sequencing and/or targeted NGS assay deep sequencing. Cases for which sufficient nucleic acid amounts are available will undergo additional analyses including whole genome sequencing, mRNA-sequencing, miRNA sequencing, promoter methylation analysis, and SNP analysis.

Other: Laboratory Biomarker Analysis

Interventions

Laboratory Biomarker Analysis OTHER

Undergo sequencing and SNP analysis

Ancillary-Correlative (molecular profiling)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with cancer participating in the Exceptional Cases Initiative

You may qualify if:

• Documented exceptional response, defined as patients meeting the following criteria:
• Complete response to a regimen in which complete response is expected in \< 10% of similarly treated patients
• Partial response (PR) \> 6 months in a regimen in which PRs \> 6 months are expected in \< 10% of patients with similar disease treated with same or similar regimen
• Complete response (CR) or PR of unusual duration, such that the internal review committee considers it to be an exceptional response; examples below:
• PR of duration \> 3 x the median expected PR duration (in cases where PR is expected in \> 10% of patients with the same disease treated with the same regimen)
• CR or duration \> 3 x the median expected CR duration (in cases where CR may be seen in \> 10% of patients with same disease treated with same regimen)
• The observed duration of CR (or PR) is longer than expected for 90% of patients with same disease treated with same regimen
• Note: it is not required that the patient be enrolled on a clinical trial when the exceptional response was observed
• Reports of radiologic scans or other evidence documenting response will be submitted for review; cases where response is not assessable (e.g. adjuvant treatment) will not be eligible because the outcome can not be attributed to a specific treatment
• Treatment history must be available, for prior treatment and for the drug to which the exceptional response occurred
• Patient must meet consent criteria; this requires: (i) current exceptional responder (ER) consent by a living participant not lost to follow-up, (ii) prior consent for future research by a participant not known to be deceased, but lost to follow-up, or (iii) if patient is deceased and did not decline to participate in research at the time of tissue removal for any tissue that would be used in this study, then no consent is required
• Tumor sample available that meets study requirements
• Required tumor samples MUST exist and be able to be submitted; investigators wishing to submit samples must not have made agreements that would prohibit the free use of data from such samples; the National Cancer Institute (NCI) will provide investigators with a letter for the collaborator amending their existing agreement to allow for the case to be submitted
• Tumor tissue from prior to administration of the drug to which the exceptional response occurred is required; ideally this sample will have been collected just prior to treatment, but other prior tissue will be considered; tissue may be fresh frozen or formalin-fixed paraffin embedded
• Tumor tissue amount must be at least a core biopsy, and meet minimum specimen requirements

You may not qualify if:

• Patient's response did not meet criteria for an exceptional response
• Patient's treatment regimen is expected to lead to CR or durable PR in \> 10% of patients
• Patient's duration of response is not \> 3 x expected median length of response
• Response not evaluable or not able to be attributed to systemic treatment (e.g. adjuvant treatment)
• Patient refused consent for use of tissue for research activities included in the exceptional responders study
• Tumor sample from prior to the exceptional response is not available, or does not meet quality metrics

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (73)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Kaiser Permanente-Fresno

Fresno, California, 93720, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

Kaiser Permanente-Richmond

Richmond, California, 94801, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051, United States

Location

Kaiser Permanente-Santa Rosa

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente-Stockton

Stockton, California, 95210, United States

Location

Kaiser Permanente-Walnut Creek

Walnut Creek, California, 94596, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Greenwich Hospital

Greenwich, Connecticut, 06830, United States

Location

Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

John B Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

South Georgia Medical Center/Pearlman Cancer Center

Valdosta, Georgia, 31602, United States

Location

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

Location

Rush MD Anderson Cancer Center

Chicago, Illinois, 60612, United States

Location

Presence Resurrection Medical Center

Chicago, Illinois, 60631, United States

Location

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Springfield Clinic

Springfield, Illinois, 62702, United States

Location

Physicians' Clinic of Iowa PC

Cedar Rapids, Iowa, 52402, United States

Location

York Hospital

York Village, Maine, 03909, United States

Location

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, 48106, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Trinity Health Medical Center - Brighton

Brighton, Michigan, 48114, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

Location

UP Health System Hematology Oncology Marquette

Marquette, Michigan, 49855, United States

Location

UP Health System Marquette

Marquette, Michigan, 49855, United States

Location

Henry Ford Health Providence Southfield Hospital

Southfield, Michigan, 48075, United States

Location

Saint Francis Medical Center

Cape Girardeau, Missouri, 63703, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Benefis Sletten Cancer Institute

Great Falls, Montana, 59405, United States

Location

Portsmouth Regional Hospital

Portsmouth, New Hampshire, 03802, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Cancer Centers of Southwest Oklahoma Research

Lawton, Oklahoma, 73505, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Kaiser Permanente Northwest

Portland, Oregon, 97227, United States

Location

Reading Hospital McGlinn Cancer Institute at Phoenixville

Phoenixville, Pennsylvania, 19460, United States

Location

Chester County Hospital

West Chester, Pennsylvania, 19380, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, 29605, United States

Location

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605, United States

Location

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, 29672, United States

Location

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

Location

Wellmont Holston Valley Hospital and Medical Center

Kingsport, Tennessee, 37660, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

WVUH-Berkely Medical Center

Martinsburg, West Virginia, 25401, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

Aurora Medical Center in Summit

Summit, Wisconsin, 53066, United States

Location

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, 53188, United States

Location

Related Publications (1)

• Moore KN, Mannel RS. Is the NCI MATCH trial a match for gynecologic oncology? Gynecol Oncol. 2016 Jan;140(1):161-6. doi: 10.1016/j.ygyno.2015.11.003. Epub 2015 Nov 14.

  PMID: 26586415 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Tissue, blood, and buccal cells

MeSH Terms

Conditions

Neoplasms

Study Officials

• S. P Ivy

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 18, 2014
• Study Start: September 24, 2014
• Primary Completion: March 4, 2021
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-03

Locations

US (73)