Onderzoek naar RAS(ON)-remmers bij patiënten met vaste maagtumoren
Een platformonderzoek naar RAS(ON)-remmers bij patiënten met vaste maagtumoren
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
Studie Overzicht
Toestand
Conditie
Gedetailleerde beschrijving
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
Inschrijving (Geschat)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studiecontact
- Naam: Revolution Medicines
- Telefoonnummer: 1-844-2-REVMED
- E-mail: medinfo@revmed.com
Studie Locaties
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Arizona
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Chandler, Arizona, Verenigde Staten, 85224
- Werving
- Ironwood Cancer and Research Centers
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Contact:
- Research Department
- Telefoonnummer: 480-398-7671
- E-mail: research@ironwoodcrc.com
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Phoenix, Arizona, Verenigde Staten, 85054
- Werving
- Mayo Clinic Hospital
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Contact:
- Telefoonnummer: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
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Scottsdale, Arizona, Verenigde Staten, 85258
- Werving
- HonorHealth Research Institute
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Contact:
- Andrea House
- Telefoonnummer: 480-323-1364
- E-mail: ahouse@honorhealth.com
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California
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La Jolla, California, Verenigde Staten, 92093
- Werving
- UC San Diego Moores Cancer Center
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Contact:
- Andrea Galfo
- Telefoonnummer: 858-822-4500
- E-mail: agalfo@health.com
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Los Angeles, California, Verenigde Staten, 90404
- Werving
- UCLA Hematology/Oncology- Santa Monica
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Contact:
- Jenna Davis
- Telefoonnummer: 16128 (310) 633-8400
- E-mail: jldavis@mednet.ucla.edu
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Los Angeles, California, Verenigde Staten, 90048
- Werving
- Cedars-Sinai Cancer at Cedars-Sinai Medical Center
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Contact:
- Naomi Geier
- Telefoonnummer: 310-423-4693
- E-mail: naomi.geier@cshs.org
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Colorado
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Aurora, Colorado, Verenigde Staten, 88045
- Werving
- University of Colorado Hospital-Anschutz Cancer Pavilion
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Contact:
- Emily Harper
- Telefoonnummer: (303) 724-9407
- E-mail: Emily.harper@cuanschutz.edu
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Connecticut
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New Haven, Connecticut, Verenigde Staten, 06520
- Werving
- Yale-New Haven Hospital-Yale Cancer Center
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Contact:
- Kwasi Boateng
- Telefoonnummer: 203-314-7948
- E-mail: Kwasi.Boateng@yale.edu
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Contact:
- Stefanie Diaz
- Telefoonnummer: 475-227-1088
- E-mail: Stefanie.Diaz@yale.edu
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Florida
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Jacksonville, Florida, Verenigde Staten, 32224
- Werving
- Mayo Clinic Cancer Center
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Contact:
- Telefoonnummer: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
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Tampa, Florida, Verenigde Staten, 33612
- Werving
- Moffitt Cancer Center
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Contact:
- Nilufar Aliyeva
- Telefoonnummer: 813.745.4436
- E-mail: Nilufar.Aliyeva@moffitt.org
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Kansas
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Westwood, Kansas, Verenigde Staten, 66205
- Werving
- The University of Kansas Clinical Research Center
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Contact:
- Telefoonnummer: 913-945-7552
- E-mail: CTNurseNav@kumc.edu
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21287
- Werving
- The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
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Contact:
- Joann Santmyer
- Telefoonnummer: 410-614-3644
- E-mail: giclinicaltrials@jhmi.edu
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Contact:
- Colleen Apostol
- Telefoonnummer: 410-614-3644
- E-mail: giclinicaltrials@jhmi.edu
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02114
- Werving
- Massachusetts General Hospital
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Contact:
- Aparna Parikh
- Telefoonnummer: (617) 724-4000
- E-mail: Aparna.Parikh@MGH.HARVARD.EDU
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Contact:
- Bennett Caughey
- Telefoonnummer: (617) 724-4000
- E-mail: bcaughey1@mgb.org
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Boston, Massachusetts, Verenigde Staten, 02215
- Werving
- Dana Farber Cancer Institute
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Contact:
- Charlotte Healy
- Telefoonnummer: 617-632-5728
- E-mail: charlotte_healy@dfci.harvard.edu
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Minnesota
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Rochester, Minnesota, Verenigde Staten, 55905
- Werving
- Mayo Clinic
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Contact:
- Telefoonnummer: 855-776-0015
- E-mail: mayocliniccancerstudies@mayo.edu
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Nebraska
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Omaha, Nebraska, Verenigde Staten, 68198
- Werving
- University of Nebraska Medical Center
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Contact:
- Mahdi Hassan
- Telefoonnummer: 402-559-1947
- E-mail: mhassan@unmc.edu
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Contact:
- Monica Davis
- Telefoonnummer: 402-559-9466
- E-mail: mondavis@unmc.edu
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Omaha, Nebraska, Verenigde Staten, 68130
- Werving
- Nebraska Cancer Specialists
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Contact:
- Ashley Servais
- Telefoonnummer: 4029552691
- E-mail: aservais@nebraskacancer.com
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Contact:
- Evan Roberts
- Telefoonnummer: 4023344773
- E-mail: eroberts@nebraskacancer.com
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New Jersey
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Morristown, New Jersey, Verenigde Staten, 07960
- Werving
- Atlantic Health System
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Contact:
- Salome Geene
- Telefoonnummer: 973-971-6373
- E-mail: salome.geene@atlantichelath.org
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Contact:
- Tracey Hilden
- Telefoonnummer: 973-971-7889
- E-mail: tracey.hilden@atlantichealth.org
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New York
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Lake Success, New York, Verenigde Staten, 11042
- Werving
- Northwell Health / RJ Zuckerberg Cancer Center
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Contact:
- Deeksha Kaura
- Telefoonnummer: 516-734-8906
- E-mail: GITrialReferral@northwell.edu
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New York, New York, Verenigde Staten, 10032
- Werving
- Columbia University Medical Center
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Contact:
- Telefoonnummer: 212-342-5162
- E-mail: cancerclinicaltrials@cumc.columbia.edu
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New York, New York, Verenigde Staten, 10065
- Werving
- Memorial Sloan Kettering Cancer Center Main Campus
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North Carolina
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Durham, North Carolina, Verenigde Staten, 27710
- Werving
- Duke University Medical Center
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Contact:
- Brooke Currier
- Telefoonnummer: 919-668-1861
- E-mail: gi-oncology-cru@dm.duke.edu
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Ohio
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Cincinnati, Ohio, Verenigde Staten, 45267
- Werving
- University of Cincinnati Medical Center
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Contact:
- Telefoonnummer: 513-584-7698
- E-mail: cancer@uchealth.com
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Oklahoma
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Oklahoma City, Oklahoma, Verenigde Staten, 73104
- Werving
- Stephenson Cancer Center
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Contact:
- Christina Caldwell
- Telefoonnummer: 48171 405-271-8001
- E-mail: Christina-Caldwell@ouhsc.edu
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104
- Werving
- Hospital of the University of Pennsylvania
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Contact:
- Jimar Hill
- Telefoonnummer: 215 349 8245
- E-mail: Jimar.Hill@pennmedicine.upenn.edu
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Tennessee
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Nashville, Tennessee, Verenigde Staten, 37203
- Werving
- SCRI Oncology Partners
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Texas
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Houston, Texas, Verenigde Staten, 77030
- Werving
- Baylor College of Medicine
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Contact:
- Henry Atencio
- Telefoonnummer: 713-798-3743
- E-mail: phase1dldccc@bcm.edu
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Contact:
- Glenn Wilson
- Telefoonnummer: 713-798-3468
- E-mail: phase1dldccc@bcm.edu
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Houston, Texas, Verenigde Staten, 77030
- Werving
- The University of Texas MD Anderson Cancer Center
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Contact:
- E-mail: GIClinicalTrials@mdanderson.org
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Irving, Texas, Verenigde Staten, 75039
- Werving
- NEXT Oncology Dallas
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Contact:
- Idara Ukpong
- Telefoonnummer: 972.893.8800
- E-mail: iukpong@nextoncology.com
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Utah
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Salt Lake City, Utah, Verenigde Staten, 84112
- Werving
- Huntsman Cancer Institute, University of Utah
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Contact:
- Susan Sharry
- Telefoonnummer: (801) 585-3453
- E-mail: (Susan.Sharry@hci.utah.edu)
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Virginia
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Fairfax, Virginia, Verenigde Staten, 22314
- Werving
- Virginia Cancer Specialists
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Contact:
- Karina Castillo
- Telefoonnummer: 571.350.8758
- E-mail: Karina.CastilloGrady@usoncology.com
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Washington
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Seattle, Washington, Verenigde Staten, 98109
- Werving
- Fred Hutchinson Cancer Center
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Contact:
- Matt Sherman
- Telefoonnummer: 206-606-6347
- E-mail: mfsherman@fredhutch.org
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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 |
|
Experimenteel: 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 |
|
Experimenteel: Subprotocol C: metastatic PDAC
RMC-6236 (QD) and gemcitabine with nab-paclitaxel |
Oral tablet IV infusion IV infusion |
|
Experimenteel: 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 |
|
Experimenteel: 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 |
|
Experimenteel: 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 |
|
Experimenteel: Subprotocol G: RAS G12D-mutated metastatic CRC
RMC-9805 (QD) and cetuximab with FOLFIRI |
IV infusion Oral Tablet IV infusion |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Adverse events (Subprotocols A-F)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: Up to 3 years
|
Up to 3 years
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Pharmacokinetics of RMC-6236 (Subprotocols A-F)
Tijdsspanne: 21 weeks
|
Blood concentration of RMC-6236 over time |
21 weeks
|
|
Pharmacokinetics of RMC-9805 (Subprotocols D-G)
Tijdsspanne: 21 weeks
|
Blood concentration of RMC-9805 over time |
21 weeks
|
|
ORR assessed by Investigator (Subprotocols A-G)
Tijdsspanne: Up to 3 years
|
Overall Response Rate per RECIST v1.1 |
Up to 3 years
|
|
DOR (Subprotocols A-G)
Tijdsspanne: Up to 3 years
|
Duration of Response per RECIST v1.1 |
Up to 3 years
|
|
DCR (Subprotocols A-G)
Tijdsspanne: Up to 3 years
|
Incidence of Response per RECIST v1.1 |
Up to 3 years
|
|
TTR (Subprotocols A-G)
Tijdsspanne: Up to 3 years
|
Time to Response per RECIST v1.1 |
Up to 3 years
|
|
PFS (Subprotocols A-G)
Tijdsspanne: Up to 3 years
|
Progression Free Survival per RECIST v1.1 |
Up to 3 years
|
|
PFS Rate at 6 and 12 Months (Subprotocol G)
Tijdsspanne: Up to 3 years
|
Up to 3 years
|
|
|
OS (Subprotocols A-F)
Tijdsspanne: Up to 3 years
|
Overall Survival |
Up to 3 years
|
|
Overall Survival Rate at 12 Months (Subprotocol G)
Tijdsspanne: Up to 3 years
|
Up to 3 years
|
|
|
Number of Participants with Adverse Events (Subprotocol G)
Tijdsspanne: Up to 3 years
|
Up to 3 years
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Study Director, Revolution Medicines
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Endocriene systeemziekten
- Neoplasmata per site
- Neoplasmata
- Darmziekten
- Neoplasmata per histologisch type
- Neoplasmata van het spijsverteringsstelsel
- Ziekten van het spijsverteringsstelsel
- Gastro-intestinale aandoeningen
- Intestinale neoplasmata
- Rectale ziekten
- Endocriene klierneoplasmata
- Alvleesklier Ziekten
- Neoplasmata, glandulair en epitheel
- Adenocarcinoom
- Colon Ziekten
- Carcinoom
- Neoplasmata, ductaal, lobulair en medullair
- Carcinoom, ductaal
- Colorectale neoplasmata
- Pancreasneoplasmata
- Gastro-intestinale neoplasmata
- Carcinoom, ductaal pancreas
- Aminozuren, peptiden en eiwitten
- Eiwitten
- Heterocyclische verbindingen, 1-ring
- Heterocyclische verbindingen
- Antilichamen, monoklonaal, gehumaniseerd
- Antilichamen, monoklonaal
- Antilichamen
- Immunoglobulinen
- Immunoproteïnen
- Bloedeiwitten
- Serum -globulines
- Globulines
- Deoxycytidine
- Cytidine
- Pyrimidine -nucleosiden
- Pyrimidines
- Bevacizumab
- Cetuximab
- Gemcitabine
- 130-nm albumine-gebonden Paclitaxel
Andere studie-ID-nummers
- RMC-GI-102
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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