Molekylär profilering i vävnadsprover från patienter med cancer som är exceptionella svar på behandling
Exceptional Responders Pilotstudie: Molekylär profilering av tumörer från cancerpatienter som är exceptionella Responders
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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Kontakter och platser
Studieorter
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California
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Duarte, California, Förenta staterna, 91010
- City of Hope Comprehensive Cancer Center
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Fresno, California, Förenta staterna, 93720
- Kaiser Permanente-Fresno
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Oakland, California, Förenta staterna, 94611
- Kaiser Permanente-Oakland
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Richmond, California, Förenta staterna, 94801
- Kaiser Permanente-Richmond
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San Francisco, California, Förenta staterna, 94158
- UCSF Medical Center-Mission Bay
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Santa Clara, California, Förenta staterna, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Rosa, California, Förenta staterna, 95403
- Kaiser Permanente-Santa Rosa
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Stockton, California, Förenta staterna, 95210
- Kaiser Permanente-Stockton
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Walnut Creek, California, Förenta staterna, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, Förenta staterna, 80045
- UCHealth University of Colorado Hospital
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Fort Collins, Colorado, Förenta staterna, 80524
- Poudre Valley Hospital
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Connecticut
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Greenwich, Connecticut, Förenta staterna, 06830
- Greenwich Hospital
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Delaware
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Newark, Delaware, Förenta staterna, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Förenta staterna, 19713
- Medical Oncology Hematology Consultants PA
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District of Columbia
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Washington D.C., District of Columbia, Förenta staterna, 20016
- Sibley Memorial Hospital
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Georgia
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Atlanta, Georgia, Förenta staterna, 30322
- Emory University Hospital/Winship Cancer Institute
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Columbus, Georgia, Förenta staterna, 31904
- John B Amos Cancer Center
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Valdosta, Georgia, Förenta staterna, 31602
- South Georgia Medical Center/Pearlman Cancer Center
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Idaho
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Boise, Idaho, Förenta staterna, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Illinois
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Chicago, Illinois, Förenta staterna, 60631
- Presence Resurrection Medical Center
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Chicago, Illinois, Förenta staterna, 60612
- Rush MD Anderson Cancer Center
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Decatur, Illinois, Förenta staterna, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Förenta staterna, 62526
- Cancer Care Specialists of Illinois - Decatur
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Evanston, Illinois, Förenta staterna, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Peoria, Illinois, Förenta staterna, 61615
- Illinois CancerCare-Peoria
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Springfield, Illinois, Förenta staterna, 62702
- Springfield Clinic
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Iowa
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Cedar Rapids, Iowa, Förenta staterna, 52402
- Physicians' Clinic of Iowa PC
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Maine
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York Village, Maine, Förenta staterna, 03909
- York Hospital
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Maryland
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Bethesda, Maryland, Förenta staterna, 20892
- NCI - Center for Cancer Research
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Bethesda, Maryland, Förenta staterna, 20892
- National Cancer Institute Developmental Therapeutics Clinic
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Michigan
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Ann Arbor, Michigan, Förenta staterna, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Förenta staterna, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Brighton, Michigan, Förenta staterna, 48114
- Trinity Health Medical Center - Brighton
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Detroit, Michigan, Förenta staterna, 48201
- Wayne State University/Karmanos Cancer Institute
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Grand Rapids, Michigan, Förenta staterna, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Marquette, Michigan, Förenta staterna, 49855
- UP Health System Marquette
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Marquette, Michigan, Förenta staterna, 49855
- UP Health System Hematology Oncology Marquette
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Southfield, Michigan, Förenta staterna, 48075
- Henry Ford Health Providence Southfield Hospital
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Missouri
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Cape Girardeau, Missouri, Förenta staterna, 63703
- Saint Francis Medical Center
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Springfield, Missouri, Förenta staterna, 65807
- CoxHealth South Hospital
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Springfield, Missouri, Förenta staterna, 65804
- Mercy Hospital Springfield
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St Louis, Missouri, Förenta staterna, 63110
- Washington University School of Medicine
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St Louis, Missouri, Förenta staterna, 63131
- Missouri Baptist Medical Center
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St Louis, Missouri, Förenta staterna, 63141
- Mercy Hospital Saint Louis
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Montana
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Great Falls, Montana, Förenta staterna, 59405
- Benefis Sletten Cancer Institute
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New Hampshire
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Portsmouth, New Hampshire, Förenta staterna, 03802
- Portsmouth Regional Hospital
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New Mexico
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Albuquerque, New Mexico, Förenta staterna, 87106
- University of New Mexico Cancer Center
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New York
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Rochester, New York, Förenta staterna, 14642
- University of Rochester
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North Carolina
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Durham, North Carolina, Förenta staterna, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, Förenta staterna, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, Förenta staterna, 58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus, Ohio, Förenta staterna, 43214
- Riverside Methodist Hospital
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Oklahoma
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Lawton, Oklahoma, Förenta staterna, 73505
- Cancer Centers of Southwest Oklahoma Research
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Oklahoma City, Oklahoma, Förenta staterna, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, Förenta staterna, 97227
- Kaiser Permanente Northwest
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Pennsylvania
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Phoenixville, Pennsylvania, Förenta staterna, 19460
- Reading Hospital McGlinn Cancer Institute at Phoenixville
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West Chester, Pennsylvania, Förenta staterna, 19380
- Chester County Hospital
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West Reading, Pennsylvania, Förenta staterna, 19611
- Reading Hospital
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South Carolina
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Greenville, South Carolina, Förenta staterna, 29605
- Prisma Health Cancer Institute - Faris
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Greenville, South Carolina, Förenta staterna, 29605
- Prisma Health Cancer Institute - Butternut
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Seneca, South Carolina, Förenta staterna, 29672
- Prisma Health Cancer Institute - Seneca
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South Dakota
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Sioux Falls, South Dakota, Förenta staterna, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Sioux Falls, South Dakota, Förenta staterna, 57104
- Sanford Cancer Center Oncology Clinic
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Tennessee
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Kingsport, Tennessee, Förenta staterna, 37660
- Wellmont Holston Valley Hospital and Medical Center
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Texas
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Houston, Texas, Förenta staterna, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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Houston, Texas, Förenta staterna, 77030
- Ben Taub General Hospital
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San Antonio, Texas, Förenta staterna, 78229
- University of Texas Health Science Center at San Antonio
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Utah
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Salt Lake City, Utah, Förenta staterna, 84112
- Huntsman Cancer Institute/University of Utah
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Virginia
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Charlottesville, Virginia, Förenta staterna, 22908
- University of Virginia Cancer Center
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West Virginia
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Martinsburg, West Virginia, Förenta staterna, 25401
- WVUH-Berkely Medical Center
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Wisconsin
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Madison, Wisconsin, Förenta staterna, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Summit, Wisconsin, Förenta staterna, 53066
- Aurora Medical Center in Summit
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Waukesha, Wisconsin, Förenta staterna, 53188
- UW Cancer Center at ProHealth Care
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Testmetod
Studera befolkning
Patients with cancer participating in the Exceptional Cases Initiative
Beskrivning
Inclusion Criteria:
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Documented exceptional response, defined as patients meeting the following criteria:
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Complete response to a regimen in which complete response is expected in < 10% of similarly treated patients
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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
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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
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Note: it is not required that the patient be enrolled on a clinical trial when the exceptional response was observed
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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
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Treatment history must be available, for prior treatment and for the drug to which the exceptional response occurred
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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
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Tumor sample available that meets study requirements
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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
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Encouraged: normal tissue sample: (optional): blood or other specimen source for germline sequencing
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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
Studieplan
Hur är studien utformad?
Designdetaljer
- Observationsmodeller: CASE_CONTROL
- Tidsperspektiv: RETROSPECTIVE
Kohorter och interventioner
Grupp / Kohort |
Intervention / Behandling |
|---|---|
|
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. |
Undergo sequencing and SNP analysis |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Molecular features in tissue samples from patients who were exceptional responders
Tidsram: Baseline
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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
|
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Putative mechanisms of action of the treatments that the patients received when they experienced their exceptional responses
Tidsram: Baseline
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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
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Number of cases identified as potential exceptional responders
Tidsram: Baseline
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Statistical analyses will be primarily descriptive. |
Baseline
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Percentage of identified potential cases confirmed to be exceptional responders
Tidsram: Baseline
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Statistical analyses will be primarily descriptive. |
Baseline
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Percentage of confirmed exceptional responders for which adequate tissue with appropriate informed consent is acquired
Tidsram: Baseline
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Statistical analyses will be primarily descriptive. |
Baseline
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Percentage of acquired cases with tissue for which at least the minimum molecular characterization is successfully obtained
Tidsram: Baseline
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Statistical analyses will be primarily descriptive. |
Baseline
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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
Tidsram: Baseline
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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
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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
Tidsram: Baseline
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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
|
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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
Tidsram: Baseline
|
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
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: S. P Ivy, National Cancer Institute (NCI)
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Beräknad)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- NCI-2014-01585
- UM1CA186704 (U.S.S. NIH-anslag/kontrakt)
- 9671 (Annan identifierare: CTEP)
- NCI-2014-01585 (Registeridentifierare: CTRP (Clinical Trial Reporting Program))
- 9671 (Annan identifierare: National Cancer Institute)
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