Molekylær profilering i vævsprøver fra patienter med kræft, som er exceptionelle respondere på behandling
Exceptional Responders Pilotundersøgelse: Molekylær profilering af tumorer fra kræftpatienter, der er exceptionelle respondere
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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Kontakter og lokationer
Studiesteder
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California
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Duarte, California, Forenede Stater, 91010
- City of Hope Comprehensive Cancer Center
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Fresno, California, Forenede Stater, 93720
- Kaiser Permanente-Fresno
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Oakland, California, Forenede Stater, 94611
- Kaiser Permanente-Oakland
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Richmond, California, Forenede Stater, 94801
- Kaiser Permanente-Richmond
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San Francisco, California, Forenede Stater, 94158
- UCSF Medical Center-Mission Bay
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Santa Clara, California, Forenede Stater, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Rosa, California, Forenede Stater, 95403
- Kaiser Permanente-Santa Rosa
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Stockton, California, Forenede Stater, 95210
- Kaiser Permanente-Stockton
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Walnut Creek, California, Forenede Stater, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- UCHealth University of Colorado Hospital
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Fort Collins, Colorado, Forenede Stater, 80524
- Poudre Valley Hospital
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Connecticut
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Greenwich, Connecticut, Forenede Stater, 06830
- Greenwich Hospital
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Delaware
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Newark, Delaware, Forenede Stater, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Forenede Stater, 19713
- Medical Oncology Hematology Consultants PA
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20016
- Sibley Memorial Hospital
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322
- Emory University Hospital/Winship Cancer Institute
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Columbus, Georgia, Forenede Stater, 31904
- John B Amos Cancer Center
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Valdosta, Georgia, Forenede Stater, 31602
- South Georgia Medical Center/Pearlman Cancer Center
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Idaho
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Boise, Idaho, Forenede Stater, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Illinois
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Chicago, Illinois, Forenede Stater, 60631
- Presence Resurrection Medical Center
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Chicago, Illinois, Forenede Stater, 60612
- Rush MD Anderson Cancer Center
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Decatur, Illinois, Forenede Stater, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Forenede Stater, 62526
- Cancer Care Specialists of Illinois - Decatur
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Evanston, Illinois, Forenede Stater, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Peoria, Illinois, Forenede Stater, 61615
- Illinois CancerCare-Peoria
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Springfield, Illinois, Forenede Stater, 62702
- Springfield Clinic
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Iowa
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Cedar Rapids, Iowa, Forenede Stater, 52402
- Physicians' Clinic of Iowa PC
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Maine
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York Village, Maine, Forenede Stater, 03909
- York Hospital
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Maryland
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Bethesda, Maryland, Forenede Stater, 20892
- NCI - Center for Cancer Research
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Bethesda, Maryland, Forenede Stater, 20892
- National Cancer Institute Developmental Therapeutics Clinic
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Forenede Stater, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Brighton, Michigan, Forenede Stater, 48114
- Trinity Health Medical Center - Brighton
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Detroit, Michigan, Forenede Stater, 48201
- Wayne State University/Karmanos Cancer Institute
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Grand Rapids, Michigan, Forenede Stater, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Marquette, Michigan, Forenede Stater, 49855
- UP Health System Marquette
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Marquette, Michigan, Forenede Stater, 49855
- UP Health System Hematology Oncology Marquette
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Southfield, Michigan, Forenede Stater, 48075
- Henry Ford Health Providence Southfield Hospital
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Missouri
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Cape Girardeau, Missouri, Forenede Stater, 63703
- Saint Francis Medical Center
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Springfield, Missouri, Forenede Stater, 65807
- CoxHealth South Hospital
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Springfield, Missouri, Forenede Stater, 65804
- Mercy Hospital Springfield
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St Louis, Missouri, Forenede Stater, 63110
- Washington University School of Medicine
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St Louis, Missouri, Forenede Stater, 63131
- Missouri Baptist Medical Center
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St Louis, Missouri, Forenede Stater, 63141
- Mercy Hospital Saint Louis
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Montana
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Great Falls, Montana, Forenede Stater, 59405
- Benefis Sletten Cancer Institute
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New Hampshire
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Portsmouth, New Hampshire, Forenede Stater, 03802
- Portsmouth Regional Hospital
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New Mexico
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Albuquerque, New Mexico, Forenede Stater, 87106
- University of New Mexico Cancer Center
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New York
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Rochester, New York, Forenede Stater, 14642
- University of Rochester
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North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, Forenede Stater, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, Forenede Stater, 58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus, Ohio, Forenede Stater, 43214
- Riverside Methodist Hospital
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Oklahoma
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Lawton, Oklahoma, Forenede Stater, 73505
- Cancer Centers of Southwest Oklahoma Research
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, Forenede Stater, 97227
- Kaiser Permanente Northwest
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Pennsylvania
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Phoenixville, Pennsylvania, Forenede Stater, 19460
- Reading Hospital McGlinn Cancer Institute at Phoenixville
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West Chester, Pennsylvania, Forenede Stater, 19380
- Chester County Hospital
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West Reading, Pennsylvania, Forenede Stater, 19611
- Reading Hospital
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South Carolina
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Greenville, South Carolina, Forenede Stater, 29605
- Prisma Health Cancer Institute - Faris
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Greenville, South Carolina, Forenede Stater, 29605
- Prisma Health Cancer Institute - Butternut
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Seneca, South Carolina, Forenede Stater, 29672
- Prisma Health Cancer Institute - Seneca
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South Dakota
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Sioux Falls, South Dakota, Forenede Stater, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Sioux Falls, South Dakota, Forenede Stater, 57104
- Sanford Cancer Center Oncology Clinic
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Tennessee
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Kingsport, Tennessee, Forenede Stater, 37660
- Wellmont Holston Valley Hospital and Medical Center
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Texas
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Houston, Texas, Forenede Stater, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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Houston, Texas, Forenede Stater, 77030
- Ben Taub General Hospital
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San Antonio, Texas, Forenede Stater, 78229
- University of Texas Health Science Center at San Antonio
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Utah
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Salt Lake City, Utah, Forenede Stater, 84112
- Huntsman Cancer Institute/University of Utah
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Virginia
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Charlottesville, Virginia, Forenede Stater, 22908
- University of Virginia Cancer Center
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West Virginia
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Martinsburg, West Virginia, Forenede Stater, 25401
- WVUH-Berkely Medical Center
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Wisconsin
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Madison, Wisconsin, Forenede Stater, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Summit, Wisconsin, Forenede Stater, 53066
- Aurora Medical Center in Summit
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Waukesha, Wisconsin, Forenede Stater, 53188
- UW Cancer Center at ProHealth Care
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Patients with cancer participating in the Exceptional Cases Initiative
Beskrivelse
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
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: CASE_CONTROL
- Tidsperspektiver: RETROSPECTIVE
Antal grupper/kohorter
Kohorter og interventioner
Gruppe / kohorteGruppe / kohorte |
Intervention / BehandlingIntervention / Behandling |
|---|---|
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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 |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Molecular features in tissue samples from patients who were exceptional responders
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
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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
Tidsramme: 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
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Ledende efterforsker: S. P Ivy, National Cancer Institute (NCI)
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Anslået)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- NCI-2014-01585
- UM1CA186704 (U.S. NIH-bevilling/kontrakt)
- 9671 (Anden identifikator: CTEP)
- NCI-2014-01585 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 9671 (Anden identifikator: National Cancer Institute)
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