Molekulares Profiling in Gewebeproben von Krebspatienten, die hervorragend auf die Behandlung ansprechen
Exceptional Responders-Pilotstudie: Molekulare Profilerstellung von Tumoren von Krebspatienten, die außergewöhnliche Responder sind
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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Kontakte und Standorte
Studienorte
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California
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Duarte, California, Vereinigte Staaten, 91010
- City of Hope Comprehensive Cancer Center
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Fresno, California, Vereinigte Staaten, 93720
- Kaiser Permanente-Fresno
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Oakland, California, Vereinigte Staaten, 94611
- Kaiser Permanente-Oakland
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Richmond, California, Vereinigte Staaten, 94801
- Kaiser Permanente-Richmond
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San Francisco, California, Vereinigte Staaten, 94158
- UCSF Medical Center-Mission Bay
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Santa Clara, California, Vereinigte Staaten, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Rosa, California, Vereinigte Staaten, 95403
- Kaiser Permanente-Santa Rosa
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Stockton, California, Vereinigte Staaten, 95210
- Kaiser Permanente-Stockton
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Walnut Creek, California, Vereinigte Staaten, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, Vereinigte Staaten, 80045
- UCHealth University of Colorado Hospital
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Fort Collins, Colorado, Vereinigte Staaten, 80524
- Poudre Valley Hospital
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Connecticut
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Greenwich, Connecticut, Vereinigte Staaten, 06830
- Greenwich Hospital
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Delaware
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Newark, Delaware, Vereinigte Staaten, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Vereinigte Staaten, 19713
- Medical Oncology Hematology Consultants PA
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District of Columbia
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Washington D.C., District of Columbia, Vereinigte Staaten, 20016
- Sibley Memorial Hospital
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Georgia
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Atlanta, Georgia, Vereinigte Staaten, 30322
- Emory University Hospital/Winship Cancer Institute
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Columbus, Georgia, Vereinigte Staaten, 31904
- John B Amos Cancer Center
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Valdosta, Georgia, Vereinigte Staaten, 31602
- South Georgia Medical Center/Pearlman Cancer Center
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Idaho
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Boise, Idaho, Vereinigte Staaten, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Illinois
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Chicago, Illinois, Vereinigte Staaten, 60631
- Presence Resurrection Medical Center
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Chicago, Illinois, Vereinigte Staaten, 60612
- Rush MD Anderson Cancer Center
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Decatur, Illinois, Vereinigte Staaten, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Vereinigte Staaten, 62526
- Cancer Care Specialists of Illinois - Decatur
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Evanston, Illinois, Vereinigte Staaten, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Peoria, Illinois, Vereinigte Staaten, 61615
- Illinois CancerCare-Peoria
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Springfield, Illinois, Vereinigte Staaten, 62702
- Springfield Clinic
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Iowa
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Cedar Rapids, Iowa, Vereinigte Staaten, 52402
- Physicians' Clinic of Iowa PC
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Maine
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York Village, Maine, Vereinigte Staaten, 03909
- York Hospital
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Maryland
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Bethesda, Maryland, Vereinigte Staaten, 20892
- NCI - Center for Cancer Research
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Bethesda, Maryland, Vereinigte Staaten, 20892
- National Cancer Institute Developmental Therapeutics Clinic
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Michigan
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Ann Arbor, Michigan, Vereinigte Staaten, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Vereinigte Staaten, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Brighton, Michigan, Vereinigte Staaten, 48114
- Trinity Health Medical Center - Brighton
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Detroit, Michigan, Vereinigte Staaten, 48201
- Wayne State University/Karmanos Cancer Institute
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Grand Rapids, Michigan, Vereinigte Staaten, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Marquette, Michigan, Vereinigte Staaten, 49855
- UP Health System Marquette
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Marquette, Michigan, Vereinigte Staaten, 49855
- UP Health System Hematology Oncology Marquette
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Southfield, Michigan, Vereinigte Staaten, 48075
- Henry Ford Health Providence Southfield Hospital
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Missouri
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Cape Girardeau, Missouri, Vereinigte Staaten, 63703
- Saint Francis Medical Center
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Springfield, Missouri, Vereinigte Staaten, 65807
- CoxHealth South Hospital
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Springfield, Missouri, Vereinigte Staaten, 65804
- Mercy Hospital Springfield
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St Louis, Missouri, Vereinigte Staaten, 63110
- Washington University School of Medicine
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St Louis, Missouri, Vereinigte Staaten, 63131
- Missouri Baptist Medical Center
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St Louis, Missouri, Vereinigte Staaten, 63141
- Mercy Hospital Saint Louis
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Montana
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Great Falls, Montana, Vereinigte Staaten, 59405
- Benefis Sletten Cancer Institute
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New Hampshire
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Portsmouth, New Hampshire, Vereinigte Staaten, 03802
- Portsmouth Regional Hospital
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New Mexico
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Albuquerque, New Mexico, Vereinigte Staaten, 87106
- University of New Mexico Cancer Center
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New York
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Rochester, New York, Vereinigte Staaten, 14642
- University of Rochester
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North Carolina
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Durham, North Carolina, Vereinigte Staaten, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, Vereinigte Staaten, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, Vereinigte Staaten, 58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus, Ohio, Vereinigte Staaten, 43214
- Riverside Methodist Hospital
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Oklahoma
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Lawton, Oklahoma, Vereinigte Staaten, 73505
- Cancer Centers of Southwest Oklahoma Research
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Oklahoma City, Oklahoma, Vereinigte Staaten, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, Vereinigte Staaten, 97227
- Kaiser Permanente Northwest
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Pennsylvania
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Phoenixville, Pennsylvania, Vereinigte Staaten, 19460
- Reading Hospital McGlinn Cancer Institute at Phoenixville
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West Chester, Pennsylvania, Vereinigte Staaten, 19380
- Chester County Hospital
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West Reading, Pennsylvania, Vereinigte Staaten, 19611
- Reading Hospital
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South Carolina
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Greenville, South Carolina, Vereinigte Staaten, 29605
- Prisma Health Cancer Institute - Faris
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Greenville, South Carolina, Vereinigte Staaten, 29605
- Prisma Health Cancer Institute - Butternut
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Seneca, South Carolina, Vereinigte Staaten, 29672
- Prisma Health Cancer Institute - Seneca
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South Dakota
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Sioux Falls, South Dakota, Vereinigte Staaten, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Sioux Falls, South Dakota, Vereinigte Staaten, 57104
- Sanford Cancer Center Oncology Clinic
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Tennessee
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Kingsport, Tennessee, Vereinigte Staaten, 37660
- Wellmont Holston Valley Hospital and Medical Center
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Texas
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Houston, Texas, Vereinigte Staaten, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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Houston, Texas, Vereinigte Staaten, 77030
- Ben Taub General Hospital
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San Antonio, Texas, Vereinigte Staaten, 78229
- University of Texas Health Science Center at San Antonio
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Utah
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Salt Lake City, Utah, Vereinigte Staaten, 84112
- Huntsman Cancer Institute/University of Utah
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Virginia
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Charlottesville, Virginia, Vereinigte Staaten, 22908
- University of Virginia Cancer Center
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West Virginia
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Martinsburg, West Virginia, Vereinigte Staaten, 25401
- WVUH-Berkely Medical Center
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Wisconsin
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Madison, Wisconsin, Vereinigte Staaten, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Summit, Wisconsin, Vereinigte Staaten, 53066
- Aurora Medical Center in Summit
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Waukesha, Wisconsin, Vereinigte Staaten, 53188
- UW Cancer Center at ProHealth Care
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
Patients with cancer participating in the Exceptional Cases Initiative
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Beobachtungsmodelle: CASE_CONTROL
- Zeitperspektiven: RETROSPECTIVE
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
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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 |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Molecular features in tissue samples from patients who were exceptional responders
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Hauptermittler: S. P Ivy, National Cancer Institute (NCI)
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Geschätzt)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- NCI-2014-01585
- UM1CA186704 (US NIH Stipendium/Vertrag)
- 9671 (Andere Kennung: CTEP)
- NCI-2014-01585 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
- 9671 (Andere Kennung: National Cancer Institute)
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