Clinical trial NCT02243592: Molecular Profiling in Tissue Samples From Patients With Cancer Who Are Exceptional Responders to Treatment
Official title: Exceptional Responders Pilot Study: Molecular Profiling of Tumors From Cancer Patients Who Are Exceptional Responders
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Malignant Neoplasm
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2014-09-18
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with cancer participating in the Exceptional Cases Initiative

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Molecular features in tissue samples from patients who were exceptional responders
timeFrame: Baseline
measure: Putative mechanisms of action of the treatments that the patients received when they experienced their exceptional responses
timeFrame: Baseline
measure: Number of cases identified as potential exceptional responders
timeFrame: Baseline
measure: Percentage of identified potential cases confirmed to be exceptional responders
timeFrame: Baseline
measure: Percentage of confirmed exceptional responders for which adequate tissue with appropriate informed consent is acquired
timeFrame: Baseline
measure: Percentage of acquired cases with tissue for which at least the minimum molecular characterization is successfully obtained
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Fresno
country: United States
facility: Kaiser Permanente-Fresno
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Richmond
country: United States
facility: Kaiser Permanente-Richmond
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente-Santa Rosa
state: California
city: Stockton
country: United States
facility: Kaiser Permanente-Stockton
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente-Walnut Creek
state: California
city: Aurora
country: United States
facility: UCHealth University of Colorado Hospital
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Greenwich
country: United States
facility: Greenwich Hospital
state: Connecticut
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Columbus
country: United States
facility: John B Amos Cancer Center
state: Georgia
city: Valdosta
country: United States
facility: South Georgia Medical Center/Pearlman Cancer Center
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Presence Resurrection Medical Center
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois - Decatur
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Cedar Rapids
country: United States
facility: Physicians' Clinic of Iowa PC
state: Iowa
city: York
country: United States
facility: York Hospital
state: Maine
city: Bethesda
country: United States
facility: National Cancer Institute Developmental Therapeutics Clinic
state: Maryland
city: Bethesda
country: United States
facility: NCI - Center for Cancer Research
state: Maryland
city: Ann Arbor
country: United States
facility: Trinity Health Saint Joseph Mercy Hospital Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Brighton
country: United States
facility: Trinity Health Medical Center - Brighton
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Marquette
country: United States
facility: UP Health System Hematology Oncology Marquette
state: Michigan
city: Marquette
country: United States
facility: UP Health System Marquette
state: Michigan
city: Southfield
country: United States
facility: Henry Ford Health Providence Southfield Hospital
state: Michigan
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Portsmouth
country: United States
facility: Portsmouth Regional Hospital
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Lawton
country: United States
facility: Cancer Centers of Southwest Oklahoma Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: Phoenixville
country: United States
facility: Phoenixville Hospital
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Butternut
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health Cancer Institute - Seneca
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Kingsport
country: United States
facility: Wellmont Holston Valley Hospital and Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Martinsburg
country: United States
facility: WVUH-Berkely Medical Center
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
Study officials:
affiliation: National Cancer Institute (NCI)
name: S. P Ivy
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.