Undersøgelse af RAS(ON)-hæmmere hos patienter med gastrointestinale faste tumorer
En platformsundersøgelse af RAS(ON)-hæmmere hos patienter med faste gastrointestinale tumorer
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
Studieoversigt
Status
Betingelser
Detaljeret 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.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Revolution Medicines
- Telefonnummer: 1-844-2-REVMED
- E-mail: medinfo@revmed.com
Studiesteder
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Arizona
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Chandler, Arizona, Forenede Stater, 85224
- Rekruttering
- Ironwood Cancer and Research Centers
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Kontakt:
- Research Department
- Telefonnummer: 480-398-7671
- E-mail: research@ironwoodcrc.com
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Phoenix, Arizona, Forenede Stater, 85054
- Rekruttering
- Mayo Clinic Hospital
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Kontakt:
- Telefonnummer: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
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Scottsdale, Arizona, Forenede Stater, 85258
- Rekruttering
- HonorHealth Research Institute
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Kontakt:
- Andrea House
- Telefonnummer: 480-323-1364
- E-mail: ahouse@honorhealth.com
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California
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La Jolla, California, Forenede Stater, 92093
- Rekruttering
- UC San Diego Moores Cancer Center
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Kontakt:
- Andrea Galfo
- Telefonnummer: 858-822-4500
- E-mail: agalfo@health.com
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Los Angeles, California, Forenede Stater, 90404
- Rekruttering
- UCLA Hematology/Oncology- Santa Monica
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Kontakt:
- Jenna Davis
- Telefonnummer: 16128 (310) 633-8400
- E-mail: jldavis@mednet.ucla.edu
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Los Angeles, California, Forenede Stater, 90048
- Rekruttering
- Cedars-Sinai Cancer at Cedars-Sinai Medical Center
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Kontakt:
- Naomi Geier
- Telefonnummer: 310-423-4693
- E-mail: naomi.geier@cshs.org
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Colorado
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Aurora, Colorado, Forenede Stater, 88045
- Rekruttering
- University of Colorado Hospital-Anschutz Cancer Pavilion
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Kontakt:
- Emily Harper
- Telefonnummer: (303) 724-9407
- E-mail: Emily.harper@cuanschutz.edu
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Connecticut
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New Haven, Connecticut, Forenede Stater, 06520
- Rekruttering
- Yale-New Haven Hospital-Yale Cancer Center
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Kontakt:
- Kwasi Boateng
- Telefonnummer: 203-314-7948
- E-mail: Kwasi.Boateng@yale.edu
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Kontakt:
- Stefanie Diaz
- Telefonnummer: 475-227-1088
- E-mail: Stefanie.Diaz@yale.edu
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Florida
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Jacksonville, Florida, Forenede Stater, 32224
- Rekruttering
- Mayo Clinic Cancer Center
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Kontakt:
- Telefonnummer: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
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Tampa, Florida, Forenede Stater, 33612
- Rekruttering
- Moffitt Cancer Center
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Kontakt:
- Nilufar Aliyeva
- Telefonnummer: 813.745.4436
- E-mail: Nilufar.Aliyeva@moffitt.org
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Kansas
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Westwood, Kansas, Forenede Stater, 66205
- Rekruttering
- The University of Kansas Clinical Research Center
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Kontakt:
- Telefonnummer: 913-945-7552
- E-mail: CTNurseNav@kumc.edu
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Maryland
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Baltimore, Maryland, Forenede Stater, 21287
- Rekruttering
- The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
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Kontakt:
- Joann Santmyer
- Telefonnummer: 410-614-3644
- E-mail: giclinicaltrials@jhmi.edu
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Kontakt:
- Colleen Apostol
- Telefonnummer: 410-614-3644
- E-mail: giclinicaltrials@jhmi.edu
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02114
- Rekruttering
- Massachusetts General Hospital
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Kontakt:
- Aparna Parikh
- Telefonnummer: (617) 724-4000
- E-mail: Aparna.Parikh@MGH.HARVARD.EDU
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Kontakt:
- Bennett Caughey
- Telefonnummer: (617) 724-4000
- E-mail: bcaughey1@mgb.org
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Boston, Massachusetts, Forenede Stater, 02215
- Rekruttering
- Dana Farber Cancer Institute
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Kontakt:
- Charlotte Healy
- Telefonnummer: 617-632-5728
- E-mail: charlotte_healy@dfci.harvard.edu
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Rekruttering
- Mayo Clinic
-
Kontakt:
- Telefonnummer: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
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Nebraska
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Omaha, Nebraska, Forenede Stater, 68198
- Rekruttering
- University of Nebraska Medical Center
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Kontakt:
- Mahdi Hassan
- Telefonnummer: 402-559-1947
- E-mail: mhassan@unmc.edu
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Kontakt:
- Monica Davis
- Telefonnummer: 402-559-9466
- E-mail: mondavis@unmc.edu
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Omaha, Nebraska, Forenede Stater, 68130
- Rekruttering
- Nebraska Cancer Specialists
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Kontakt:
- Ashley Servais
- Telefonnummer: 4029552691
- E-mail: aservais@nebraskacancer.com
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Kontakt:
- Evan Roberts
- Telefonnummer: 4023344773
- E-mail: eroberts@nebraskacancer.com
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New Jersey
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Morristown, New Jersey, Forenede Stater, 07960
- Rekruttering
- Atlantic Health System
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Kontakt:
- Salome Geene
- Telefonnummer: 973-971-6373
- E-mail: salome.geene@atlantichelath.org
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Kontakt:
- Tracey Hilden
- Telefonnummer: 973-971-7889
- E-mail: tracey.hilden@atlantichealth.org
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New York
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Lake Success, New York, Forenede Stater, 11042
- Rekruttering
- Northwell Health / RJ Zuckerberg Cancer Center
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Kontakt:
- Deeksha Kaura
- Telefonnummer: 516-734-8906
- E-mail: GITrialReferral@northwell.edu
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New York, New York, Forenede Stater, 10032
- Rekruttering
- Columbia University Medical Center
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Kontakt:
- Telefonnummer: 212-342-5162
- E-mail: cancerclinicaltrials@cumc.columbia.edu
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New York, New York, Forenede Stater, 10065
- Rekruttering
- Memorial Sloan Kettering Cancer Center Main Campus
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North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Rekruttering
- Duke University Medical Center
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Kontakt:
- Brooke Currier
- Telefonnummer: 919-668-1861
- E-mail: gi-oncology-cru@dm.duke.edu
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Ohio
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Cincinnati, Ohio, Forenede Stater, 45267
- Rekruttering
- University of Cincinnati Medical Center
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Kontakt:
- Telefonnummer: 513-584-7698
- E-mail: cancer@uchealth.com
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- Rekruttering
- Stephenson Cancer Center
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Kontakt:
- Christina Caldwell
- Telefonnummer: 48171 405-271-8001
- E-mail: Christina-Caldwell@ouhsc.edu
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Rekruttering
- Hospital of the University of Pennsylvania
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Kontakt:
- Jimar Hill
- Telefonnummer: 215 349 8245
- E-mail: Jimar.Hill@pennmedicine.upenn.edu
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37203
- Rekruttering
- SCRI Oncology Partners
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Texas
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Houston, Texas, Forenede Stater, 77030
- Rekruttering
- Baylor College of Medicine
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Kontakt:
- Henry Atencio
- Telefonnummer: 713-798-3743
- E-mail: phase1dldccc@bcm.edu
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Kontakt:
- Glenn Wilson
- Telefonnummer: 713-798-3468
- E-mail: phase1dldccc@bcm.edu
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Houston, Texas, Forenede Stater, 77030
- Rekruttering
- The University of Texas MD Anderson Cancer Center
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Kontakt:
- E-mail: GIClinicalTrials@mdanderson.org
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Irving, Texas, Forenede Stater, 75039
- Rekruttering
- NEXT Oncology Dallas
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Kontakt:
- Idara Ukpong
- Telefonnummer: 972.893.8800
- E-mail: iukpong@nextoncology.com
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Utah
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Salt Lake City, Utah, Forenede Stater, 84112
- Rekruttering
- Huntsman Cancer Institute, University of Utah
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Kontakt:
- Susan Sharry
- Telefonnummer: (801) 585-3453
- E-mail: (Susan.Sharry@hci.utah.edu)
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Virginia
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Fairfax, Virginia, Forenede Stater, 22314
- Rekruttering
- Virginia Cancer Specialists
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Kontakt:
- Karina Castillo
- Telefonnummer: 571.350.8758
- E-mail: Karina.CastilloGrady@usoncology.com
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Washington
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Seattle, Washington, Forenede Stater, 98109
- Rekruttering
- Fred Hutchinson Cancer Center
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Kontakt:
- Matt Sherman
- Telefonnummer: 206-606-6347
- E-mail: mfsherman@fredhutch.org
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
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 undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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 |
|
Eksperimentel: 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 |
|
Eksperimentel: Subprotocol C: metastatic PDAC
RMC-6236 (QD) and gemcitabine with nab-paclitaxel |
Oral tablet IV infusion IV infusion |
|
Eksperimentel: 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 |
|
Eksperimentel: 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 |
|
Eksperimentel: 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 |
|
Eksperimentel: Subprotocol G: RAS G12D-mutated metastatic CRC
RMC-9805 (QD) and cetuximab with FOLFIRI |
IV infusion Oral Tablet IV infusion |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
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 |
Foranstaltningsbeskrivelse |
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
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Study Director, Revolution Medicines
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i det endokrine system
- Neoplasmer efter sted
- Neoplasmer
- Tarmsygdomme
- Neoplasmer efter histologisk type
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Intestinale neoplasmer
- Endetarmssygdomme
- Neoplasmer i endokrine kirtler
- Pancreassygdomme
- Neoplasmer, kirtel og epitel
- Adenocarcinom
- Tyktarmssygdomme
- Karcinom
- Neoplasmer, duktale, lobulære og medullære
- Carcinom, Ductal
- Kolorektale neoplasmer
- Bugspytkirtel neoplasmer
- Gastrointestinale neoplasmer
- Karcinom, bugspytkirtelduktal
- Aminosyrer, peptider og proteiner
- Proteiner
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Antistoffer, monoklonal, humaniseret
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Deoxycytidin
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Bevacizumab
- Cetuximab
- Gemcitabin
- 130-nm albuminbundet paclitaxel
Andre undersøgelses-id-numre
- RMC-GI-102
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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