Studie av RAS(ON)-hemmere hos pasienter med faste gastrointestinale svulster
En plattformstudie av RAS(ON)-hemmere hos pasienter med faste gastrointestinale svulster
The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents.
The current subprotocols include the following:
Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens
Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6
Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel
Subprotocol D: RMC-9805 with or without RMC-6236 + 5-fluorouracil-based regimens
Subprotocol E: RMC-9805 with or without RMC-6236 + cetuximab with or without mFOLFOX6
Subprotocol F: RMC-9805 with or without RMC-6236 + gemcitabine + nab-paclitaxel
Subprotocol G: RMC-9805 + cetuximab + FOLFIRI
Studieoversikt
Status
Forhold
Detaljert beskrivelse
The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents to be evaluated in patients with RAS-mutated solid tumors with a focus on GI cancers.
This is an open-label platform study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC) or with novel agents, and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with RAS mutations will be specified in each subprotocol.
Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with treatment-naïve unresectable or metastatic colorectal cancer or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter study of RMC-6236 in combination with cetuximab with or without mFOLFOX6 in patients with unresectable or metastatic colorectal cancer or patients with previously treated or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol D is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with 5-fluorouracil-based regimens in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol E is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with cetuximab-based therapies with or without mFOLFOX6 in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol F is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with RAS G12D-mutant metastatic pancreatic ductal adenocarcinoma. Subprotocol G is an open-label, multicenter study of RMC-9805 with cetuximab and FOLFIRI in patients with previously treated, RAS G12D-mutated metastatic colorectal cancer.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Revolution Medicines
- Telefonnummer: 1-844-2-REVMED
- E-post: medinfo@revmed.com
Studiesteder
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Arizona
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Chandler, Arizona, Forente stater, 85224
- Rekruttering
- Ironwood Cancer and Research Centers
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Ta kontakt med:
- Research Department
- Telefonnummer: 480-398-7671
- E-post: research@ironwoodcrc.com
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Phoenix, Arizona, Forente stater, 85054
- Rekruttering
- Mayo Clinic Hospital
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Ta kontakt med:
- Telefonnummer: 855-776-0015
- E-post: mayocliniccancerstudies@mayo.edu
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Scottsdale, Arizona, Forente stater, 85258
- Rekruttering
- HonorHealth Research Institute
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Ta kontakt med:
- Andrea House
- Telefonnummer: 480-323-1364
- E-post: ahouse@honorhealth.com
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California
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La Jolla, California, Forente stater, 92093
- Rekruttering
- UC San Diego Moores Cancer Center
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Ta kontakt med:
- Andrea Galfo
- Telefonnummer: 858-822-4500
- E-post: agalfo@health.com
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Los Angeles, California, Forente stater, 90404
- Rekruttering
- UCLA Hematology/Oncology- Santa Monica
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Ta kontakt med:
- Jenna Davis
- Telefonnummer: 16128 (310) 633-8400
- E-post: jldavis@mednet.ucla.edu
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Los Angeles, California, Forente stater, 90048
- Rekruttering
- Cedars-Sinai Cancer at Cedars-Sinai Medical Center
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Ta kontakt med:
- Naomi Geier
- Telefonnummer: 310-423-4693
- E-post: naomi.geier@cshs.org
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Colorado
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Aurora, Colorado, Forente stater, 88045
- Rekruttering
- University of Colorado Hospital-Anschutz Cancer Pavilion
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Ta kontakt med:
- Emily Harper
- Telefonnummer: (303) 724-9407
- E-post: Emily.harper@cuanschutz.edu
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Connecticut
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New Haven, Connecticut, Forente stater, 06520
- Rekruttering
- Yale-New Haven Hospital-Yale Cancer Center
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Ta kontakt med:
- Kwasi Boateng
- Telefonnummer: 203-314-7948
- E-post: Kwasi.Boateng@yale.edu
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Ta kontakt med:
- Stefanie Diaz
- Telefonnummer: 475-227-1088
- E-post: Stefanie.Diaz@yale.edu
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Florida
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Jacksonville, Florida, Forente stater, 32224
- Rekruttering
- Mayo Clinic Cancer Center
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Ta kontakt med:
- Telefonnummer: 855-776-0015
- E-post: mayocliniccancerstudies@mayo.edu
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Tampa, Florida, Forente stater, 33612
- Rekruttering
- Moffitt Cancer Center
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Ta kontakt med:
- Nilufar Aliyeva
- Telefonnummer: 813.745.4436
- E-post: Nilufar.Aliyeva@moffitt.org
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Kansas
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Westwood, Kansas, Forente stater, 66205
- Rekruttering
- The University of Kansas Clinical Research Center
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Ta kontakt med:
- Telefonnummer: 913-945-7552
- E-post: CTNurseNav@kumc.edu
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Maryland
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Baltimore, Maryland, Forente stater, 21287
- Rekruttering
- The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
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Ta kontakt med:
- Joann Santmyer
- Telefonnummer: 410-614-3644
- E-post: giclinicaltrials@jhmi.edu
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Ta kontakt med:
- Colleen Apostol
- Telefonnummer: 410-614-3644
- E-post: giclinicaltrials@jhmi.edu
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Massachusetts
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Boston, Massachusetts, Forente stater, 02114
- Rekruttering
- Massachusetts General Hospital
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Ta kontakt med:
- Aparna Parikh
- Telefonnummer: (617) 724-4000
- E-post: Aparna.Parikh@MGH.HARVARD.EDU
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Ta kontakt med:
- Bennett Caughey
- Telefonnummer: (617) 724-4000
- E-post: bcaughey1@mgb.org
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Boston, Massachusetts, Forente stater, 02215
- Rekruttering
- Dana Farber Cancer Institute
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Ta kontakt med:
- Charlotte Healy
- Telefonnummer: 617-632-5728
- E-post: charlotte_healy@dfci.harvard.edu
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Minnesota
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Rochester, Minnesota, Forente stater, 55905
- Rekruttering
- Mayo Clinic
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Ta kontakt med:
- Telefonnummer: 855-776-0015
- E-post: mayocliniccancerstudies@mayo.edu
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Nebraska
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Omaha, Nebraska, Forente stater, 68198
- Rekruttering
- University of Nebraska Medical Center
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Ta kontakt med:
- Mahdi Hassan
- Telefonnummer: 402-559-1947
- E-post: mhassan@unmc.edu
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Ta kontakt med:
- Monica Davis
- Telefonnummer: 402-559-9466
- E-post: mondavis@unmc.edu
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Omaha, Nebraska, Forente stater, 68130
- Rekruttering
- Nebraska Cancer Specialists
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Ta kontakt med:
- Ashley Servais
- Telefonnummer: 4029552691
- E-post: aservais@nebraskacancer.com
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Ta kontakt med:
- Evan Roberts
- Telefonnummer: 4023344773
- E-post: eroberts@nebraskacancer.com
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New Jersey
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Morristown, New Jersey, Forente stater, 07960
- Rekruttering
- Atlantic Health System
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Ta kontakt med:
- Salome Geene
- Telefonnummer: 973-971-6373
- E-post: salome.geene@atlantichelath.org
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Ta kontakt med:
- Tracey Hilden
- Telefonnummer: 973-971-7889
- E-post: tracey.hilden@atlantichealth.org
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New York
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Lake Success, New York, Forente stater, 11042
- Rekruttering
- Northwell Health / RJ Zuckerberg Cancer Center
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Ta kontakt med:
- Deeksha Kaura
- Telefonnummer: 516-734-8906
- E-post: GITrialReferral@northwell.edu
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New York, New York, Forente stater, 10032
- Rekruttering
- Columbia University Medical Center
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Ta kontakt med:
- Telefonnummer: 212-342-5162
- E-post: cancerclinicaltrials@cumc.columbia.edu
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New York, New York, Forente stater, 10065
- Rekruttering
- Memorial Sloan Kettering Cancer Center Main Campus
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North Carolina
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Durham, North Carolina, Forente stater, 27710
- Rekruttering
- Duke University Medical Center
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Ta kontakt med:
- Brooke Currier
- Telefonnummer: 919-668-1861
- E-post: gi-oncology-cru@dm.duke.edu
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Ohio
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Cincinnati, Ohio, Forente stater, 45267
- Rekruttering
- University of Cincinnati Medical Center
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Ta kontakt med:
- Telefonnummer: 513-584-7698
- E-post: cancer@uchealth.com
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Oklahoma
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Oklahoma City, Oklahoma, Forente stater, 73104
- Rekruttering
- Stephenson Cancer Center
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Ta kontakt med:
- Christina Caldwell
- Telefonnummer: 48171 405-271-8001
- E-post: Christina-Caldwell@ouhsc.edu
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- Rekruttering
- Hospital of the University of Pennsylvania
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Ta kontakt med:
- Jimar Hill
- Telefonnummer: 215 349 8245
- E-post: Jimar.Hill@pennmedicine.upenn.edu
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Tennessee
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Nashville, Tennessee, Forente stater, 37203
- Rekruttering
- SCRI Oncology Partners
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Texas
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Houston, Texas, Forente stater, 77030
- Rekruttering
- Baylor College of Medicine
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Ta kontakt med:
- Henry Atencio
- Telefonnummer: 713-798-3743
- E-post: phase1dldccc@bcm.edu
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Ta kontakt med:
- Glenn Wilson
- Telefonnummer: 713-798-3468
- E-post: phase1dldccc@bcm.edu
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Houston, Texas, Forente stater, 77030
- Rekruttering
- The University of Texas MD Anderson Cancer Center
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Ta kontakt med:
- E-post: GIClinicalTrials@mdanderson.org
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Irving, Texas, Forente stater, 75039
- Rekruttering
- NEXT Oncology Dallas
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Ta kontakt med:
- Idara Ukpong
- Telefonnummer: 972.893.8800
- E-post: iukpong@nextoncology.com
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Utah
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Salt Lake City, Utah, Forente stater, 84112
- Rekruttering
- Huntsman Cancer Institute, University of Utah
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Ta kontakt med:
- Susan Sharry
- Telefonnummer: (801) 585-3453
- E-post: (Susan.Sharry@hci.utah.edu)
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Virginia
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Fairfax, Virginia, Forente stater, 22314
- Rekruttering
- Virginia Cancer Specialists
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Ta kontakt med:
- Karina Castillo
- Telefonnummer: 571.350.8758
- E-post: Karina.CastilloGrady@usoncology.com
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Washington
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Seattle, Washington, Forente stater, 98109
- Rekruttering
- Fred Hutchinson Cancer Center
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Ta kontakt med:
- Matt Sherman
- Telefonnummer: 206-606-6347
- E-post: mfsherman@fredhutch.org
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
All Patients (unless otherwise noted):
- ≥ 18 years of age
- ECOG PS is 0 to 1
- Adequate organ function as outlined by the study
- Pathologically or cytologically documented pancreatic carcinoma or poorly differentiated pancreatic carcinoma with metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A, B, C and G)
- Presence of RAS G12D mutation (Subprotocol D, E, F, G)
Exclusion Criteria:
All Patients:
- Primary central nervous system (CNS) tumors
- Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
- Major surgery within 28 days of first dose
Other inclusion/exclusion criteria may apply.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and bevacizumab with 5-fluorouracil-based regimens |
Oral tablet IV infusion IV infusion IV infusion |
|
Eksperimentell: Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-6236 (QD) and cetuximab with or without mFOLFOX6 |
Oral tablet IV infusion IV infusion |
|
Eksperimentell: Subprotocol C: metastatic PDAC
RMC-6236 (QD) and gemcitabine with nab-paclitaxel |
Oral tablet IV infusion IV infusion |
|
Eksperimentell: Subprotocol D: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and bevacizumab with 5-fluorouracil- based regimens |
Oral tablet IV infusion IV infusion IV infusion Oral Tablet |
|
Eksperimentell: Subprotocol E: RAS G12D-mutated unresectable or metastatic CRC or metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and cetuximab with or without mFOLFOX6 |
Oral tablet IV infusion IV infusion Oral Tablet |
|
Eksperimentell: Subprotocol F: RAS G12D-mutated metastatic PDAC
RMC-9805 (QD or BID) with or without RMC-6236 (QD), and gemcitabine with nab-paclitaxel |
Oral tablet IV infusion IV infusion Oral Tablet |
|
Eksperimentell: Subprotocol G: RAS G12D-mutated metastatic CRC
RMC-9805 (QD) and cetuximab with FOLFIRI |
IV infusion Oral Tablet IV infusion |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Adverse events (Subprotocols A-F)
Tidsramme: Up to 3 years
|
Evaluate the safety and tolerability in the study population characterized by incidence, abnormal laboratory assessments, severity, and seriousness of adverse events in relation to the study treatment. |
Up to 3 years
|
|
Dose limiting toxicities (Subprotocols A-F)
Tidsramme: 28 days
|
Number of participants with dose limiting toxicities |
28 days
|
|
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by Blinded Independent Central Review (BICR)(Subprotocol G)
Tidsramme: Up to 3 years
|
Up to 3 years
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Pharmacokinetics of RMC-6236 (Subprotocols A-F)
Tidsramme: 21 weeks
|
Blood concentration of RMC-6236 over time |
21 weeks
|
|
Pharmacokinetics of RMC-9805 (Subprotocols D-G)
Tidsramme: 21 weeks
|
Blood concentration of RMC-9805 over time |
21 weeks
|
|
ORR assessed by Investigator (Subprotocols A-G)
Tidsramme: Up to 3 years
|
Overall Response Rate per RECIST v1.1 |
Up to 3 years
|
|
DOR (Subprotocols A-G)
Tidsramme: Up to 3 years
|
Duration of Response per RECIST v1.1 |
Up to 3 years
|
|
DCR (Subprotocols A-G)
Tidsramme: Up to 3 years
|
Incidence of Response per RECIST v1.1 |
Up to 3 years
|
|
TTR (Subprotocols A-G)
Tidsramme: Up to 3 years
|
Time to Response per RECIST v1.1 |
Up to 3 years
|
|
PFS (Subprotocols A-G)
Tidsramme: Up to 3 years
|
Progression Free Survival per RECIST v1.1 |
Up to 3 years
|
|
PFS Rate at 6 and 12 Months (Subprotocol G)
Tidsramme: Up to 3 years
|
Up to 3 years
|
|
|
OS (Subprotocols A-F)
Tidsramme: Up to 3 years
|
Overall Survival |
Up to 3 years
|
|
Overall Survival Rate at 12 Months (Subprotocol G)
Tidsramme: Up to 3 years
|
Up to 3 years
|
|
|
Number of Participants with Adverse Events (Subprotocol G)
Tidsramme: Up to 3 years
|
Up to 3 years
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Study Director, Revolution Medicines
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i det endokrine systemet
- Neoplasmer etter nettsted
- Neoplasmer
- Tarmsykdommer
- Neoplasmer etter histologisk type
- Neoplasmer i fordøyelsessystemet
- Sykdommer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Intestinale neoplasmer
- Rektale sykdommer
- Neoplasmer i endokrine kjertel
- Pankreassykdommer
- Neoplasmer, kjertel og epitel
- Adenokarsinom
- Kolonsykdommer
- Karsinom
- Neoplasmer, duktale, lobulære og medullære
- Karsinom, Ductal
- Kolorektale neoplasmer
- Neoplasmer i bukspyttkjertelen
- Gastrointestinale neoplasmer
- Karsinom, bukspyttkjertelduktal
- Aminosyrer, peptider og proteiner
- Proteiner
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Antistoffer, monoklonalt, humanisert
- Antistoffer, monoklonalt
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Deoxycytidine
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Bevacizumab
- Cetuximab
- Gemcitabin
- 130-nm albuminbundet paclitaxel
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- RMC-GI-102
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