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

June 15, 2026 updated by: Cardiff Oncology

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
110

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic - Arizona
      • Tucson, Arizona, United States, 85724
        • The University of Arizona Cancer Center
    • Arkansas
      • Jonesboro, Arkansas, United States, 72401
        • St. Bernards Medical Center
      • Springdale, Arkansas, United States, 72762
        • Highlands Oncology Group
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center - Bakersfield
      • Fountain Valley, California, United States, 92708
        • Orange Coast Memorial Medical Center
      • La Jolla, California, United States, 92037
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine-Hematology/Oncology
      • Los Angeles, California, United States, 90089
        • Norris Comprehensive Cancer Center
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
      • Torrance, California, United States, 90505
        • Torrance Memorial Physician Network - Cancer Care and Infusion Center
      • Whittier, California, United States, 90602
        • PIH Health
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Cancer Institute
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Florida
      • Stuart, Florida, United States, 34994
        • Cleveland Clinic Martin Health
    • Hawaii
      • Honolulu, Hawaii, United States, 96819
        • Kaiser Permanente
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Fort Wayne Medical Oncology and Hematology
    • Kansas
      • Westwood, Kansas, United States, 66205
        • The University of Kansas Cancer Center - Westwood
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine Center for Advanced Medicine
    • Nevada
      • Las Vegas, Nevada, United States, 89119
        • CCCN
    • New York
      • New York, New York, United States, 10016
        • Manhattan Hematology Oncology (MHO) Research Foundation, Inc.
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Trihealth Kenwood
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Wexner Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Health Network
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • West Cancer Clinic
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • Houston, Texas, United States, 77024
        • Oncology Consultants, PA
    • Utah
      • Salt Lake City, Utah, United States, 84124
        • Utah Cancer Specialists
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Richmond, Virginia, United States, 23298
        • VCU Massey Cancer Center
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Onvansertib
Oral capsule
Drug: FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
Drug: Bevacizumab
IV Infusion
Experimental: 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.
Drug: Onvansertib
Oral capsule
Drug: FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
Drug: Bevacizumab
IV Infusion
Active Comparator: Standard of Care (SOC)
Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
Drug: FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
Drug: Bevacizumab
IV Infusion
Experimental: 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.
Drug: Onvansertib
Oral capsule
Drug: Bevacizumab
IV Infusion
Drug: FOLFOX
FOLFOX (leucovorin + fluorouracil [5-FU] + oxaliplatin) as intravenous (IV) infusion
Experimental: 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.
Drug: Onvansertib
Oral capsule
Drug: Bevacizumab
IV Infusion
Drug: FOLFOX
FOLFOX (leucovorin + fluorouracil [5-FU] + oxaliplatin) as intravenous (IV) infusion
Active Comparator: Standard of Care
Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
Drug: Bevacizumab
IV Infusion
Drug: FOLFOX
FOLFOX (leucovorin + fluorouracil [5-FU] + oxaliplatin) as intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to approximately 1 year
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Up to approximately 1 year
PFS defined as the time from the date of randomization to the earliest documented disease progression per RECIST version 1.1, or death due to any cause, as determined by blinded independent central review.
Up to approximately 1 year
Duration of Response (DOR)
Time Frame: Up to approximately 1 year
DOR defined as the time from the date of first documentation of objective tumor response (CR or PR) to the earliest documented disease progression per RECIST version 1.1, or death due to any cause, as determined by blinded independent central review.
Up to approximately 1 year
Number of Participants with an Adverse Event (AE)
Time Frame: Up to approximately 1 year
Type, incidence, causality and severity of AEs based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Clinically significant changes from baseline in vital signs, laboratory parameters, electrocardiograms (ECGs), weight, and Eastern Cooperative Oncology Group (ECOG) performance status will be recorded as AEs.
Up to approximately 1 year
Disease Control Rate (DCR)
Time Frame: Up to approximately 1 year
DCR defined as CR plus PR plus stable disease (SD), as determined by independent central review.
Up to approximately 1 year
Overall Survival (OS)
Time Frame: Up to approximately 1 year
OS defined as the time from drug administration to death due to any cause.
Up to approximately 1 year
Overall Response (OR)
Time Frame: Up to approximately 1 year
Defined as CR or PR, PFS, DCR, DOR, and OS associated with a reduction in circulating tumor DNA (ctDNA) mutation allele frequency (MAF).
Up to approximately 1 year
Maximum Concentration (Cmax) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab
Time Frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Area Under the Plasma Concentration Curve (AUC) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab
Time Frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Trough Concentration (Ctrough) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab
Time Frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Efficacy: Exposure Response Evaluation of Onvansertib
Time Frame: Up to approximately 1 year
Up to approximately 1 year
Safety: Exposure Response Evaluation of Onvansertib
Time Frame: Up to approximately 1 year
Up to approximately 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cardiff Oncology

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 30, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 15, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CRDF-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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