Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
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| ClinicalTrials.gov Identifier: NCT03634982 |
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Recruitment Status :
Recruiting
First Posted : August 17, 2018
Last Update Posted : September 10, 2019
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Sponsor:
Revolution Medicines, Inc.
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.
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Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumors | Drug: RMC-4630 | Phase 1 |
This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 240 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors |
| Actual Study Start Date : | September 28, 2018 |
| Estimated Primary Completion Date : | October 1, 2021 |
| Estimated Study Completion Date : | October 1, 2021 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: RMC-4630
RMC-4630 for oral administration
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Drug: RMC-4630
RMC-4630 for oral administration |
Primary Outcome Measures :
- Number of participants with adverse events (AEs) [ Time Frame: up to 3 years ]Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy
- Number of participants with dose limiting toxicities (DLTs) [ Time Frame: 28 days ]Incidence and nature of DLTs with RMC-4630 monotherapy
Secondary Outcome Measures :
- Cmax [ Time Frame: up to 3 years ]Peak plasma concentration of RMC-4630
- Tmax [ Time Frame: up to 3 years ]Time to achieve peak plasma concentration of RMC-4630
- Area Under the Curve (AUC) [ Time Frame: up to 3 years ]Area under the plasma concentration time curve of RMC-4630
- t1/2 [ Time Frame: up to 3 years ]Elimination half-life of RMC-4630
- Accumulation Ratio [ Time Frame: up to 3 years ]Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosing
- pERK [ Time Frame: up to 3 years ]On-treatment versus baseline comparison of pharmacodynamic markers of RMC-4630 (e.g., pERK [phosphorylated form of extracellular signal-regulated kinase]) on peripheral blood mononuclear cells or newly obtained tumor samples by immunoassays or immunohistochemistry (IHC)
- Overall Response Rate (ORR) [ Time Frame: up to 3 years ]Overall response rate of RMC-4630 per RECIST v1.1
- Duration of Response (DOR) [ Time Frame: up to 3 years ]Duration of response of RMC-4630 per RECIST v1.1
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participant (male or female) ≥18 years of age
- Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: RTK mutations, amplifications or rearrangements, KRASG12, BRAF Class 3, or NF1 LOF mutations
- Adequate hematologic, hepatic and renal function
- Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
- Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
Exclusion Criteria:
- Known or suspected leptomeningeal or brain metastases or spinal cord compression
- Primary central nervous system (CNS) tumors
- Clinically significant cardiac disease
- Active, clinically significant interstitial lung disease or pneumonitis
- History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
- Known HIV infection
- Active/chronic hepatitis B or C infection
- Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
- Females who are pregnant or breastfeeding
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03634982
Contacts
| Contact: Revolution Medicines, Inc. | (650) 779-2300 | CT-Inquiries@RevolutionMedicines.com |
Locations
| United States, Arizona | |
| Honor Health Research Institute | Recruiting |
| Scottsdale, Arizona, United States, 85258 | |
| Contact: Joyce Schaffer 480-323-1791 joschaffer@honorhealth.com | |
| Principal Investigator: Michael Gordon, MD | |
| United States, California | |
| City of Hope | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: Marianna Koczywas, MD 626-256-4673 ext 83793 MKoczywas@coh.org | |
| Principal Investigator: Marianna Koczywas, MD | |
| UC Irvine - Chao Family Comprehensive Cancer Center | Recruiting |
| Orange, California, United States, 92868 | |
| Contact: Sai-Hong Ignatius Ou, MD, PhD 877-824-3627 ucstudy@uci.edu | |
| Principal Investigator: Sai-Hong Ignatius Ou, MD, PhD | |
| UC Davis Comprehensive Cancer Center | Recruiting |
| Sacramento, California, United States, 95817 | |
| Contact: Steffany Lim, CCRP 916-734-0561 sllim@ucdavis.edu | |
| Principal Investigator: Jonathan Riess, MD | |
| UC San Francisco - Helen Diller Family Comprehensive Cancer Center | Recruiting |
| San Francisco, California, United States, 94115 | |
| Contact: Gregory Nalbandian 415-514-4681 Gregory.Nalbandian@ucsf.edu | |
| Principal Investigator: Caroline McCoach, MD | |
| United States, Colorado | |
| University of Colorado Cancer Center | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| Contact: Tara Wells 720-848-0755 TARA.WELLS@CUANSCHUTZ.EDU | |
| Principal Investigator: Jose Pacheco, MD | |
| United States, Florida | |
| Sarah Cannon Research Institute - Florida Cancer Specialists | Recruiting |
| Sarasota, Florida, United States, 34232 | |
| Contact: Terri Peterson 941-377-9993 tpeterson@flcancer.com | |
| Principal Investigator: Judy Wang, MD | |
| Moffit Cancer Center | Recruiting |
| Tampa, Florida, United States, 33612 | |
| Contact: Germaine M González-Vazquez 813-745-6636 germaine.gonzalezvazquez@moffitt.org | |
| Principal Investigator: Eric Haura, MD | |
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Bryan Marion 617-632-3383 bryan_marion@dfci.harvard.edu | |
| Contact: Kaitlin Morton 617-582-8013 kaitlin_morton@dfci.harvard.edu | |
| Principal Investigator: Pasi Janne, MD, PhD | |
| United States, Oklahoma | |
| University of Oklahoma - Stephenson Cancer Center | Recruiting |
| Oklahoma City, Oklahoma, United States, 73104 | |
| Contact: Dena Suthers 405-271-8778 ext option 2 SCC-Clinical-Trials-Office@ouhsc.edu | |
| Principal Investigator: Susanna Ulahannan, MD | |
| United States, Tennessee | |
| Sarah Cannon Research Institute - Tennessee Oncology, PLLC | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Contact: Dee McComb 615-329-7478 researchreferrals@scresearch.net | |
| Principal Investigator: Howard Burris, III, MD | |
| United States, Texas | |
| University of Texas at Austin - Dell Medical School | Recruiting |
| Austin, Texas, United States, 78712 | |
| Contact: Anna Capasso 512-495-5516 anna.capasso@austin.utexas.edu | |
| Principal Investigator: Gail Eckhardt, MD | |
Sponsors and Collaborators
Revolution Medicines, Inc.
Sanofi
Investigators
| Study Director: | Revolution Medicines, Inc. | Revolution Medicines, Inc. |
| Responsible Party: | Revolution Medicines, Inc. |
| ClinicalTrials.gov Identifier: | NCT03634982 |
| Other Study ID Numbers: |
RMC-4630-01 |
| First Posted: | August 17, 2018 Key Record Dates |
| Last Update Posted: | September 10, 2019 |
| Last Verified: | September 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Revolution Medicines, Inc.:
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SHP2 PTPN11 NSCLC EGFR RTK KRAS G12 BRAF Class 3 NF1 LOF advanced solid tumor advanced solid malignancies melanoma skin cancer ovarian cancer pancreatic cancer endometrium/uterus cancer |
bladder cancer cervical cancer Carcinoma, Non-Small-Cell Lung Neoplasms, Squamous Cell Carcinoma, Squamous Cell Esophageal Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Additional relevant MeSH terms:
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Neoplasms |