Profiling molecolare in campioni di tessuto da pazienti affetti da cancro che rispondono in modo eccezionale al trattamento
Studio pilota sui responsivi eccezionali: profilo molecolare dei tumori di pazienti oncologici che rispondono in modo eccezionale
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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Contatti e Sedi
Luoghi di studio
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California
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Duarte, California, Stati Uniti, 91010
- City of Hope Comprehensive Cancer Center
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Fresno, California, Stati Uniti, 93720
- Kaiser Permanente-Fresno
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Oakland, California, Stati Uniti, 94611
- Kaiser Permanente-Oakland
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Richmond, California, Stati Uniti, 94801
- Kaiser Permanente-Richmond
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San Francisco, California, Stati Uniti, 94158
- UCSF Medical Center-Mission Bay
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Santa Clara, California, Stati Uniti, 95051
- Kaiser Permanente Medical Center - Santa Clara
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Santa Rosa, California, Stati Uniti, 95403
- Kaiser Permanente-Santa Rosa
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Stockton, California, Stati Uniti, 95210
- Kaiser Permanente-Stockton
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Walnut Creek, California, Stati Uniti, 94596
- Kaiser Permanente-Walnut Creek
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Colorado
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Aurora, Colorado, Stati Uniti, 80045
- UCHealth University of Colorado Hospital
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Fort Collins, Colorado, Stati Uniti, 80524
- Poudre Valley Hospital
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Connecticut
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Greenwich, Connecticut, Stati Uniti, 06830
- Greenwich Hospital
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Delaware
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Newark, Delaware, Stati Uniti, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Stati Uniti, 19713
- Medical Oncology Hematology Consultants PA
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District of Columbia
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Washington D.C., District of Columbia, Stati Uniti, 20016
- Sibley Memorial Hospital
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Georgia
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Atlanta, Georgia, Stati Uniti, 30322
- Emory University Hospital/Winship Cancer Institute
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Columbus, Georgia, Stati Uniti, 31904
- John B Amos Cancer Center
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Valdosta, Georgia, Stati Uniti, 31602
- South Georgia Medical Center/Pearlman Cancer Center
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Idaho
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Boise, Idaho, Stati Uniti, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Illinois
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Chicago, Illinois, Stati Uniti, 60631
- Presence Resurrection Medical Center
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Chicago, Illinois, Stati Uniti, 60612
- Rush MD Anderson Cancer Center
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Decatur, Illinois, Stati Uniti, 62526
- Decatur Memorial Hospital
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Decatur, Illinois, Stati Uniti, 62526
- Cancer Care Specialists of Illinois - Decatur
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Evanston, Illinois, Stati Uniti, 60201
- NorthShore University HealthSystem-Evanston Hospital
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Peoria, Illinois, Stati Uniti, 61615
- Illinois CancerCare-Peoria
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Springfield, Illinois, Stati Uniti, 62702
- Springfield Clinic
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Iowa
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Cedar Rapids, Iowa, Stati Uniti, 52402
- Physicians' Clinic of Iowa PC
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Maine
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York Village, Maine, Stati Uniti, 03909
- York Hospital
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Maryland
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Bethesda, Maryland, Stati Uniti, 20892
- NCI - Center for Cancer Research
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Bethesda, Maryland, Stati Uniti, 20892
- National Cancer Institute Developmental Therapeutics Clinic
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Michigan
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Ann Arbor, Michigan, Stati Uniti, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Stati Uniti, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Brighton, Michigan, Stati Uniti, 48114
- Trinity Health Medical Center - Brighton
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Detroit, Michigan, Stati Uniti, 48201
- Wayne State University/Karmanos Cancer Institute
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Grand Rapids, Michigan, Stati Uniti, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Marquette, Michigan, Stati Uniti, 49855
- UP Health System Marquette
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Marquette, Michigan, Stati Uniti, 49855
- UP Health System Hematology Oncology Marquette
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Southfield, Michigan, Stati Uniti, 48075
- Henry Ford Health Providence Southfield Hospital
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Missouri
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Cape Girardeau, Missouri, Stati Uniti, 63703
- Saint Francis Medical Center
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Springfield, Missouri, Stati Uniti, 65807
- CoxHealth South Hospital
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Springfield, Missouri, Stati Uniti, 65804
- Mercy Hospital Springfield
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St Louis, Missouri, Stati Uniti, 63110
- Washington University School of Medicine
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St Louis, Missouri, Stati Uniti, 63131
- Missouri Baptist Medical Center
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St Louis, Missouri, Stati Uniti, 63141
- Mercy Hospital Saint Louis
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Montana
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Great Falls, Montana, Stati Uniti, 59405
- Benefis Sletten Cancer Institute
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New Hampshire
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Portsmouth, New Hampshire, Stati Uniti, 03802
- Portsmouth Regional Hospital
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New Mexico
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Albuquerque, New Mexico, Stati Uniti, 87106
- University of New Mexico Cancer Center
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New York
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Rochester, New York, Stati Uniti, 14642
- University of Rochester
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North Carolina
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Durham, North Carolina, Stati Uniti, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, Stati Uniti, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, Stati Uniti, 58122
- Sanford Roger Maris Cancer Center
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Ohio
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Columbus, Ohio, Stati Uniti, 43214
- Riverside Methodist Hospital
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Oklahoma
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Lawton, Oklahoma, Stati Uniti, 73505
- Cancer Centers of Southwest Oklahoma Research
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Oklahoma City, Oklahoma, Stati Uniti, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, Stati Uniti, 97227
- Kaiser Permanente Northwest
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Pennsylvania
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Phoenixville, Pennsylvania, Stati Uniti, 19460
- Reading Hospital McGlinn Cancer Institute at Phoenixville
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West Chester, Pennsylvania, Stati Uniti, 19380
- Chester County Hospital
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West Reading, Pennsylvania, Stati Uniti, 19611
- Reading Hospital
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South Carolina
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Greenville, South Carolina, Stati Uniti, 29605
- Prisma Health Cancer Institute - Faris
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Greenville, South Carolina, Stati Uniti, 29605
- Prisma Health Cancer Institute - Butternut
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Seneca, South Carolina, Stati Uniti, 29672
- Prisma Health Cancer Institute - Seneca
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South Dakota
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Sioux Falls, South Dakota, Stati Uniti, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Sioux Falls, South Dakota, Stati Uniti, 57104
- Sanford Cancer Center Oncology Clinic
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Tennessee
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Kingsport, Tennessee, Stati Uniti, 37660
- Wellmont Holston Valley Hospital and Medical Center
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Texas
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Houston, Texas, Stati Uniti, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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Houston, Texas, Stati Uniti, 77030
- Ben Taub General Hospital
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San Antonio, Texas, Stati Uniti, 78229
- University of Texas Health Science Center at San Antonio
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Utah
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Salt Lake City, Utah, Stati Uniti, 84112
- Huntsman Cancer Institute/University of Utah
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Virginia
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Charlottesville, Virginia, Stati Uniti, 22908
- University of Virginia Cancer Center
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West Virginia
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Martinsburg, West Virginia, Stati Uniti, 25401
- WVUH-Berkely Medical Center
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Wisconsin
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Madison, Wisconsin, Stati Uniti, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Summit, Wisconsin, Stati Uniti, 53066
- Aurora Medical Center in Summit
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Waukesha, Wisconsin, Stati Uniti, 53188
- UW Cancer Center at ProHealth Care
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
Patients with cancer participating in the Exceptional Cases Initiative
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: CASE_CONTROL
- Prospettive temporali: RETROSPECTIVE
Coorti e interventi
Gruppo / Coorte |
Intervento / Trattamento |
|---|---|
|
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 |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Molecular features in tissue samples from patients who were exceptional responders
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: S. P Ivy, National Cancer Institute (NCI)
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stimato)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- NCI-2014-01585
- UM1CA186704 (Sovvenzione/contratto NIH degli Stati Uniti)
- 9671 (Altro identificatore: CTEP)
- NCI-2014-01585 (Identificatore di registro: CTRP (Clinical Trial Reporting Program))
- 9671 (Altro identificatore: National Cancer Institute)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .