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

Malignant Neoplasm Clinical Trial

Official title:

Exceptional Responders Pilot Study: Molecular Profiling of Tumors From Cancer Patients Who Are Exceptional Responders

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02243592
• Other study ID #: NCI-2014-01585
• Secondary ID: NCI-2014-0158596
• Status: Active, not recruiting
• Start date: September 24, 2014
• Est. completion date: April 2, 2025

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. To identify molecular indicators in malignant tissues from patients who were exceptional responders on clinical trials or standard systemic treatments using whole exome and/or targeted deep sequencing, as well as potentially other sequencing and other molecular characterization methods (if adequate tissue exists).

II. To explore associations between the identified molecular indicators and the putative mechanism of action of the treatment received by the patient.

III. To test the feasibility of identifying "exceptional responders", obtaining the relevant tumor and normal tissue and clinical data, and performing whole exome and/or targeted deep sequencing on these samples.

OUTLINE:

Previously collected tissue samples are analyzed via whole exome sequencing and/or targeted next generation sequencing (NGS) assay deep sequencing. Cases for which sufficient nucleic acid amounts are available will undergo additional analyses including whole genome sequencing, messenger ribonucleic acid (RNA) (mRNA)-sequencing, micro (miRNA) sequencing, promoter methylation analysis, and single nucleotide polymorphism (SNP) analysis.

Other known NCT identifiers

• NCT02496195

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: April 2, 2025
• Est. primary completion date: March 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

• Encouraged: normal tissue sample: (optional): blood or other specimen source for germline sequencing

• The tumor samples and clinical data submitted to the Exceptional Responders Database in database in Genotypes and Phenotypes (dbGaP) will need to have appropriate agreements in place to allow for the submission; the Exceptional Responders Database can accept clinical data and samples from cases enrolled on a Cancer Therapy Evaluation Program (CTEP) sponsored clinical trial and cases that were not enrolled on any clinical trial; if the response occurred on a trial that was not CTEP-sponsored, there are existing agreements between the submitting site and the pharmaceutical company; if existing agreements do not allow for the submission of sample and clinical data, the NCI will provide the investigators with a letter that allows the tissue to be used for the exceptional responders study if signed by the appropriate collaborator; the letter modifies the existing agreement to include the CTEP Intellectual Property (IP) Option language that would allow the case to be submitted to the Exceptional Responders Database; if the existing agreement cannot be modified and the letter cannot be signed, the proposed case will not be accepted; Note: as stated above, the patient does not need to have been enrolled on a clinical trial to be eligible for the exceptional responders study

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Malignant Neoplasm
• Neoplasms

Intervention

Other:
• Laboratory Biomarker Analysis
Undergo sequencing and SNP analysis

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	National Cancer Institute Developmental Therapeutics Clinic	Bethesda	Maryland
United States	NCI - Center for Cancer Research	Bethesda	Maryland
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Presence Resurrection Medical Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	John B Amos Cancer Center	Columbus	Georgia
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Greenwich Hospital	Greenwich	Connecticut
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	UP Health System Hematology Oncology Marquette	Marquette	Michigan
United States	UP Health System Marquette	Marquette	Michigan
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Portsmouth Regional Hospital	Portsmouth	New Hampshire
United States	Kaiser Permanente-Richmond	Richmond	California
United States	University of Rochester	Rochester	New York
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Clinic	Springfield	Illinois
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	South Georgia Medical Center/Pearlman Cancer Center	Valdosta	Georgia
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Reading Hospital	West Reading	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	York Hospital	York	Maine

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Number of cases identified as potential exceptional responders	Statistical analyses will be primarily descriptive.	Baseline
Primary	Percentage of identified potential cases confirmed to be exceptional responders	Statistical analyses will be primarily descriptive.	Baseline
Primary	Percentage of confirmed exceptional responders for which adequate tissue with appropriate informed consent is acquired	Statistical analyses will be primarily descriptive.	Baseline
Primary	Percentage of acquired cases with tissue for which at least the minimum molecular characterization is successfully obtained	Statistical analyses will be primarily descriptive.	Baseline
Primary	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
Primary	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
Primary	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