Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer in Adult Participants With a KRAS or NRAS Mutation
A Phase 2, Randomized, Open-label Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-line Treatment of Metastatic Colorectal Cancer in Patients With a KRAS or NRAS Mutation
1 other identifier
interventional
113
1 country
41
Brief Summary
The purpose of this study is to assess 2 different doses of onvansertib to select the lowest dose that is maximally effective, and to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of onvansertib in combination with FOLFIRI + bevacizumab or FOLFOX + bevacizumab in patients with KRAS or NRAS-mutated metastatic colorectal cancer (CRC) in the first-line setting.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2024
Typical duration for phase_2
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 24, 2023
CompletedFirst Posted
Study publicly available on registry
October 30, 2023
CompletedStudy Start
First participant enrolled
February 27, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2027
January 12, 2026
January 1, 2026
2.7 years
October 24, 2023
January 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR)
ORR defined as the proportion of participants who achieved a best overall Response (BOR) of CR or PR per RECIST Version 1.1 from randomization until disease progression, or death due to any cause, as determined by blinded independent central review.
Up to approximately 1 year
Secondary Outcomes (11)
Progression Free Survival (PFS)
Up to approximately 1 year
Duration of Response (DOR)
Up to approximately 1 year
Number of Participants with an Adverse Event (AE)
Up to approximately 1 year
Disease Control Rate (DCR)
Up to approximately 1 year
Overall Survival (OS)
Up to approximately 1 year
- +6 more secondary outcomes
Study Arms (6)
Onvansertib 20mg + Standard of Care
EXPERIMENTALParticipants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI/BEV on Day 1 and Day 15 of each 28-day treatment cycle.
Onvansertib 30 mg + Standard of Care (SOC)
EXPERIMENTALParticipants will receive 30 mg of onvansertib + on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFIRI on Day 1 and Day 15 of each 28-day treatment cycle.
Standard of Care (SOC)
ACTIVE COMPARATORParticipants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
Onvansertib 20 mg + Standard of Care
EXPERIMENTALParticipants will receive 20 mg of onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
Onvansertib 30 mg + Standard of Care
EXPERIMENTALParticipants will receive 30 mg onvansertib on Days 1 to 5 and Days 15 to 19 of each 28-day treatment cycle + FOLFOX on Day 1 and Day 15 of each 28-day treatment cycle.
Standard of Care
ACTIVE COMPARATORParticipants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
Interventions
Oral capsule
FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion
IV Infusion
FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion
Eligibility Criteria
You may qualify if:
- Histologically confirmed metastatic colorectal cancer.
- Documented KRAS or NRAS mutation.
- No previous systemic therapy in the metastatic setting.
- Participants must be willing to submit archival tissue or undergo fresh biopsy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Women of childbearing potential must use contraception or take measures to avoid pregnancy.
- Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis and other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib.
- Must have acceptable organ function
You may not qualify if:
- Concomitant KRAS or NRAS and BRAF-V600 mutation or microsatellite instability high/deficient mismatch repair.
- Prior treatment with a VEGF inhibitor, including bevacizumab or biosimilars.
- Previous oxaliplatin treatment within 12 months prior to randomization, when arm open.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Anticancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug.
- Untreated or symptomatic brain metastasis.
- Gastrointestinal (GI) disorder(s) that would significantly impede the absorption of an oral agent.
- Unable or unwilling to swallow study drug.
- Uncontrolled intercurrent illness.
- Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxalipatin.
- Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
- Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers.
- QTc \>470
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cardiff Oncologylead
- Pfizercollaborator
Study Sites (41)
Mayo Clinic - Arizona
Phoenix, Arizona, 85054, United States
The University of Arizona Cancer Center
Tucson, Arizona, 85724, United States
St. Bernards Medical Center
Jonesboro, Arkansas, 72401, United States
Highlands Oncology Group
Springdale, Arkansas, 72762, United States
Pacific Cancer Medical Center
Anaheim, California, 92801, United States
Comprehensive Blood and Cancer Center - Bakersfield
Bakersfield, California, 93309, United States
Orange Coast Memorial Medical Center
Fountain Valley, California, 92708, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92037, United States
Norris Comprehensive Cancer Center
Los Angeles, California, 90089, United States
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, 90095, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
Torrance Memorial Physician Network - Cancer Care and Infusion Center
Torrance, California, 90505, United States
PIH Health
Whittier, California, 90602, United States
Memorial Cancer Institute
Hollywood, Florida, 33021, United States
Mayo Clinic - Florida
Jacksonville, Florida, 32224, United States
Cleveland Clinic Martin Health
Stuart, Florida, 34994, United States
Kaiser Permanente
Honolulu, Hawaii, 96819, United States
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, 46804, United States
The University of Kansas Cancer Center - Westwood
Westwood, Kansas, 66205, United States
Cancer Center of Kansas
Wichita, Kansas, 67214, United States
Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
Grand Rapids, Michigan, 49503, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905, United States
Saint Luke's Hospital
Kansas City, Missouri, 64111, United States
Washington University School of Medicine Center for Advanced Medicine
St Louis, Missouri, 63110, United States
CCCN
Las Vegas, Nevada, 89119, United States
Manhattan Hematology Oncology (MHO) Research Foundation, Inc.
New York, New York, 10016, United States
Trihealth Kenwood
Cincinnati, Ohio, 45242, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103, United States
West Cancer Clinic
Germantown, Tennessee, 38138, United States
Oncology Consultants, PA
Houston, Texas, 77024, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84124, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
VCU Massey Cancer Center
Richmond, Virginia, 23298, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911, United States
Related Publications (1)
Ahn DH, Ridinger M, Cannon TL, Mendelsohn L, Starr JS, Hubbard JM, Kasi A, Barzi A, Samuelsz E, Karki A, Subramanian RA, Yemane D, Kim R, Wu CC, Croucher PJP, Smeal T, Kabbinavar FF, Lenz HJ. Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. J Clin Oncol. 2025 Mar;43(7):840-851. doi: 10.1200/JCO-24-01266. Epub 2024 Oct 30.
PMID: 39475591DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 24, 2023
First Posted
October 30, 2023
Study Start
February 27, 2024
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
January 1, 2027
Last Updated
January 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share