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

NCT ID: NCT06106308

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

113 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-27

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Colorectal Cancer CRC KRAS/NRAS Mutation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Onvansertib 20mg + Standard of Care

Participants 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.

Group Type EXPERIMENTAL

Onvansertib

Intervention Type DRUG

Oral capsule

FOLFIRI

Intervention Type DRUG

FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion

Bevacizumab

Intervention Type DRUG

IV Infusion

Onvansertib 30 mg + Standard of Care (SOC)

Participants 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.

Group Type EXPERIMENTAL

Onvansertib

Intervention Type DRUG

Oral capsule

FOLFIRI

Intervention Type DRUG

FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion

Bevacizumab

Intervention Type DRUG

IV Infusion

Standard of Care (SOC)

Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.

Group Type ACTIVE_COMPARATOR

FOLFIRI

Intervention Type DRUG

FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion

Bevacizumab

Intervention Type DRUG

IV Infusion

Onvansertib 20 mg + Standard of Care

Participants 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.

Group Type EXPERIMENTAL

Onvansertib

Intervention Type DRUG

Oral capsule

Bevacizumab

Intervention Type DRUG

IV Infusion

FOLFOX

Intervention Type DRUG

FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion

Onvansertib 30 mg + Standard of Care

Participants 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.

Group Type EXPERIMENTAL

Onvansertib

Intervention Type DRUG

Oral capsule

Bevacizumab

Intervention Type DRUG

IV Infusion

FOLFOX

Intervention Type DRUG

FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion

Standard of Care

Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

IV Infusion

FOLFOX

Intervention Type DRUG

FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion

Interventions

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Onvansertib

Oral capsule

Intervention Type DRUG

FOLFIRI

FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion

Intervention Type DRUG

Bevacizumab

IV Infusion

Intervention Type DRUG

FOLFOX

FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Cardiff Oncology

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status

The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

St. Bernards Medical Center

Jonesboro, Arkansas, United States

Site Status

Highlands Oncology Group

Springdale, Arkansas, United States

Site Status

Pacific Cancer Medical Center

Anaheim, California, United States

Site Status

Comprehensive Blood and Cancer Center - Bakersfield

Bakersfield, California, United States

Site Status

Orange Coast Memorial Medical Center

Fountain Valley, California, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA Department of Medicine-Hematology/Oncology

Los Angeles, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Torrance Memorial Physician Network - Cancer Care and Infusion Center

Torrance, California, United States

Site Status

PIH Health

Whittier, California, United States

Site Status

Memorial Cancer Institute

Hollywood, Florida, United States

Site Status

Mayo Clinic - Florida

Jacksonville, Florida, United States

Site Status

Cleveland Clinic Martin Health

Stuart, Florida, United States

Site Status

Kaiser Permanente

Honolulu, Hawaii, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

The University of Kansas Cancer Center - Westwood

Westwood, Kansas, United States

Site Status

Cancer Center of Kansas

Wichita, Kansas, United States

Site Status

Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Saint Luke's Hospital

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine Center for Advanced Medicine

St Louis, Missouri, United States

Site Status

CCCN

Las Vegas, Nevada, United States

Site Status

Manhattan Hematology Oncology (MHO) Research Foundation, Inc.

New York, New York, United States

Site Status

Trihealth Kenwood

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

West Cancer Clinic

Germantown, Tennessee, United States

Site Status

Oncology Consultants, PA

Houston, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status

VCU Massey Cancer Center

Richmond, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

ThedaCare Regional Cancer Center

Appleton, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39475591 (View on PubMed)

Other Identifiers

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CRDF-004

Identifier Type: -

Identifier Source: org_study_id

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