Molecular Profiling of Tumors From Cancer Patients Who Are Exceptional Responders

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02496195
• Other study ID #: 150146
• Secondary ID: 15-C-0146
• Status: Recruiting
• Phase: N/A
• First received: July 10, 2015
• Last updated: January 24, 2017
• Start date: June 8, 2015
• Est. completion date: June 1, 2020

Study information

• Verified date: September 26, 2016
• Source: National Institutes of Health Clinical Center (CC)
• Contact: William L Dahut, M.D.
• Phone: (301) 496-4251
• Email: dahutw[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

• Cancer can happen when a person s genes change in a way that makes cells grow uncontrolled. Researchers want to see what changes in genes might make some people with cancer respond well to some treatments. This may lead to better ways to prevent, detect, and treat cancer and other diseases.

Objectives:

• To see what changes in genes might make some people with cancer respond well to some treatments.

Eligibility:

• People who are documented exceptional responders to cancer treatment. They must have given a tumor sample that is available to researchers.

Design:

• Participants will be screened with reports of their radiology scans or other evidence that shows exceptional response.

• Participants will provide permission for researchers:

• To test cancer tissue that has previously been removed.

• To test normal tissue (blood) that has previously been collected, if available.

• To obtain data from their medical records.

• Data will be kept in an anonymous database. Other researchers may share the data.

• No new tissue will be collected from participants.

Description:

The Exceptional Responders Initiative is a pilot study to investigate the underlying molecular factors associated with exceptional treatment responses of cancer patients to drug therapies. The goal is to discover underlying molecular features that can be further investigated as potential molecular features that are predictive of benefit to a particular drug or class of drugs. Study researchers will examine molecular profiles of tumors from patients either enrolled in a clinical trial for an investigational drug(s) and who achieved an exceptional response relative to other trial participants, or who achieved an exceptional response to a non-investigational chemotherapy or approved targeted agent that is not expected. An exceptional response is defined as achievement of either a) a complete response, or b) a partial response of at least 6 months duration in a trial or treatment where the overall response rate is <10%, or a response of exceptionally long duration.

This pilot project will successfully characterize approximately 100 cases of tumor tissue and, when available, case-matched germline DNA. All samples will undergo whole exome sequencing, and/or targeted NGS assay deep sequencing. Cases for which sufficient nucleic acid amounts are available will undergo additional analyses (e.g. whole genome sequencing, messenger RNA (mRNA)-sequencing, micro (miRNA) sequencing, promoter methylation analysis, single nucleotide polymorphism (SNP) analysis, etc). Each case will be annotated with demographic and clinical information, along with follow-up information minimally sufficient to enable correlations between the molecular profiles and the drug responses. Cases will be deidentified prior to tissue being sent. All data will be de-identified and placed in a controlled-access database so other investigators may use them to gain new insights.

Clinically-annotated tissue specimens meeting the acceptance criteria will be provided by clinical cancer investigators or practitioners who choose to participate in the Exceptional Responders Initiative. Specimens will be sent to a Biospecimen Core Resource (BCR), which will perform quality control on the tissues, and will use established standard operating procedures to isolate nucleic acids. The nucleic acids will be shipped to a sequencing and characterization center at Baylor to perform designated sequencing and analysis and to Foundation Medicine Inc when enough tissue is available, for targeted deep sequencing on an analytically validated cancer panel. These findings, as well as contributed molecular profiling performed outside this effort (if possible), and correlated to exceptional responses will be made available to the broader cancer research community via a controlled-access database.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 1, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 100 Years

Eligibility

• INCLUSION CRITERIA:

1. Documented exceptional response. 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.

2. Treatment history must be available, for prior treatment and for the drug to which the exceptional response occurred.

3. Patient must meet consent criteria detailed in section VII.2.0. This requires:

(i) current 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.

4. Tumor sample available that meets study requirements.

5. 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 NCI will provide investigators with a letter for the collaborator amending their existing agreement to allow for the case to be submitted.

5.1 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

5.2 Tumor tissue amount must be at least a core biopsy, and meet minimum specimen requirements as described below in METHODS.

6. Encouraged: Normal tissue sample: (optional): Blood or other specimen source for germline sequencing.

7. The tumor samples and clinical data submitted to the Exceptional Responders Database in 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 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 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.

EXCLUSION CRITERIA:

Cases or tissue meeting these requirements will not be accepted into this study:

1. Patient's response did not meet criteria for an exceptional response

1.1 Patient's treatment regimen is expected to lead to CR or durable PR in > 10% of patients.

1.2 Patient s duration of response is not >3x expected median length of response.

1.3 Response not evaluable or not able to be attributed to systemic treatment (e.g.adjuvant treatment)

2. Patient refused consent for use of tissue for research activities included in the Exceptional Responders study.

3. Tumor sample from prior to the exceptional response is not available, or does not meet quality metrics.

Related Conditions & MeSH terms

• Cancer

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

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	To identify molecular indicators in malignant tissues from patients who were exceptional responders on clinical trials or treatments using whole exome and/or targeted deep sequencing, as well as potentially other sequencing and other molecular c...		Ongoing
Primary	To explore associations between the identified molecular indicators and the putative mechanism of action of the treatment received by the patient		Ongoing
Primary	To test the feasibility of identifying		Ongoing

External Links

•   NIH Clinical Center Detailed Web Page