Study of Onvansertib in Combination With FOLFIRI and Bevacizumab Versus FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Participants With a Kirsten Rat Sarcoma Virus Gene (KRAS) or Neuroblastoma-RAS (NRAS) Mutation

January 9, 2025 updated by: Cardiff Oncology

A Phase 2, Randomized, Open-label Study of Onvansertib in Combination With FOLFIRI and Bevacizumab Versus FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Patients With a KRAS or NRAS Mutation

The primary objective of this study is to assess the efficacy of 2 different doses of onvansertib in combination with a chemotherapy regimen of irinotecan, fluorouracil [5-FU], and leucovorin (FOLFIRI) and bevacizumab for treatment of confirmed metastatic and/or unresectable colorectal cancer (CRC) in participants with a kirsten rat sarcoma virus gene (KRAS) or neuroblastoma-RAS (NRAS) mutation who have progressed on an oxaliplatin/fluoropyrimidinebased regimen in the first-line setting.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

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.
23

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 in Arizona - Phoenix Campus
    • Arkansas
      • Little Rock, Arkansas, United States, 72205-6523
        • Central Arkansas Radiation Therapy Institute - Cancer Center
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center - Bakersfield
      • Los Alamitos, California, United States, 90720
        • Cancer and Blood Specialty Clinic
      • Los Angeles, California, United States, 90033
        • Norris Comprehensive Cancer Center
      • Orange, California, United States, 92868
        • UCI Health - Chao Family Comprehensive Cancer Center
      • Santa Monica, California, United States, 90404
        • UCLA Health - Santa Monica Parkside Cancer Care
      • Torrance, California, United States, 90505
        • Torrance Memorial Physician Network - Cancer Care and Infusion Center
      • Whittier, California, United States, 90602
        • PIH Health
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Jacksonville
      • Pembroke Pines, Florida, United States, 33028
        • Memorial Hospital West
    • 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 - Rochester
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine Center for Advanced Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Nebraska Cancer Specialists - Midwest Cancer Center - Legacy
    • New Jersey
      • Englewood, New Jersey, United States, 07631
        • Englewood Health
    • New Mexico
      • Farmington, New Mexico, United States, 87401
        • San Juan Oncology Associates
    • New York
      • New York, New York, United States, 10016
        • Manhattan Hematology Oncology Associates
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer and Research Center
      • Cincinnati, Ohio, United States, 45236
        • Trihealth Kenwood
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • West Cancer Center - East Campus
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia School of Medicine
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed metastatic and/or unresectable colorectal cancer (CRC).
  2. Documentation of a kirsten rat sarcoma virus gene (KRAS) or neuroblastoma-RAS (NRAS) mutation in exon 2, 3, or 4 in primary tumor or metastasis, assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
  3. Age ≥ 18 years.

  4. Participants with tumors that have progressed on an oxaliplatin/fluoropyrimidine--based regimen with or without bevacizumab.

    1. Participants must have had systemic therapy within 180 days of the screening visit.
    2. Participants must have, at any time previously, received oxaliplatin-based chemotherapy with or without bevacizumab (≥ 6 weeks in duration).
    3. Participants who received oxaliplatin/fluoropyrimidine-based neoadjuvant, adjuvant, and/or fluoropyrimidine maintenance or adjuvant therapy and have disease recurrence or progression > 6 months from their last dose of oxaliplatin will be required to have received oxaliplatin/fluoropyrimidine-based therapy with or without bevacizumab as first-line treatment for metastatic disease.
    4. Participants who received an oxaliplatin-based regimen in the first-line setting and discontinued oxaliplatin because of toxicity or who received oxaliplatin for maintenance therapy are eligible as long as progression occurred < 6 months after the last dose of oxaliplatin therapy for advanced metastatic disease. It is recommended that these participants be re-challenged (if feasible) with oxaliplatin/fluoropyrimidine therapy and subsequently progress prior to eligibility. Participants with oxaliplatin-related neuropathy or oxaliplatin infusion-related hypersensitivity that cannot be rechallenged with oxaliplatin are eligible.
  5. Participants must not have received prior treatment with irinotecan.
  6. FOLFIRI therapy is appropriate for the participant as determined by the Investigator.
  7. Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib. Only participants with measurable disease as defined per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) are eligible for enrollment. CT is the preferred imaging modality, but MRI is also accepted. All subsequent scans must consistently use the same imaging modality for comparison with the Screening scan throughout the study.
  8. Must have acceptable organ function
  9. Signed informed consent to provide blood sample(s) for specific correlative assays

Exclusion Criteria:

  1. Concomitant KRAS or NRAS and BRAF-V600 mutation or Microsatellite Instability High/Deficient Mismatch Repair (MSI-H/dMMR).
  2. Anti-cancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug. The exception is a single dose of radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before enrollment, provided it is not the target lesion.
  3. More than 1 prior chemotherapy regimen administered in the metastatic setting.
  4. Major surgery within 6 weeks prior to enrollment.
  5. Untreated or symptomatic brain metastasis.
  6. Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would significantly impede the absorption of an oral agent (e.g., intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
  7. Unable or unwilling to swallow study drug.
  8. Known hypersensitivity to fluoropyrimidine or leucovorin.
  9. Known hypersensitivity to irinotecan.
  10. Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.

  11. QT interval:

    1. Fridericia's correction (QTcF) > 470 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate electrocardiograms (ECGs). In the case of potentially correctible causes of QT prolongation that are readily corrected (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during Screening and that result may be used to determine eligibility.
    2. Planned concomitant use of medications known to prolong the QT/QTc interval according to institutional guidelines.
    3. Presence of risk factors for torsade de pointes, including family history of Long QT Syndrome or uncorrected hypokalemia.
  12. Use of strong cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19) inhibitors or strong CYP3A4 inducers. Participants currently receiving these agents who can be switched to alternate therapy are not excluded. Inhibitors should be stopped at least 1 week prior to the first dose of protocol therapy and inducers should be stopped at least 2 weeks prior to initiation of protocol therapy.

  13. The following are exclusion criteria for bevacizumab:

    1. History of cardiac disease: Congestive heart failure (CHF) Class II or higher according to the New York Heart Association (NYHA); active coronary artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of participants who have been receiving therapy and are deemed by the Investigator to have stable/controlled disease.
    2. Current uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite optimal medical management) and prior history of hypertensive crisis or hypertensive encephalopathy.
    3. History of arterial thrombotic or embolic events (within 6 months prior to study entry).
    4. Significant vascular disease (eg, aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease).
    5. Evidence of bleeding diathesis or clinically significant coagulopathy.
    6. Major surgical procedure (including open biopsy, significant traumatic injury, etc) within 28 days, or anticipation of the need for major surgical procedure during the study, and minor surgical procedure (excluding placement of a vascular access device) within 7 days prior to study enrollment.
    7. Proteinuria at Screening as demonstrated by urinalysis with proteinuria ≥2+ (participants discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein in 24 hours to be eligible).
    8. Abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within the past 6 months.
    9. Ongoing serious, non-healing wound, ulcer, or bone fracture
    10. Known hypersensitivity to any component of bevacizumab
    11. History of reversible posterior leukoencephalopathy syndrome

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 20 mg + Standard of Care (SOC)
Participants will receive 20 mg of onvansertib on Days 1 to 5 and 15 to 19 of a 28-day treatment cycle and SOC (FOLFIRI + bevacizumab) on Days 1 and 15 of each 28-day cycle.
Drug: Bevacizumab
IV infusion
Drug: Onvansertib
Oral capsule
Drug: FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
Experimental: Onvansertib 30 mg + Standard of Care (SOC)
Participants will receive 30 mg of onvansertib on Days 1 to 5 and 15 to 19 of a 28-day treatment cycle and SOC (FOLFIRI + bevacizumab) on Days 1 and 15 of each 28-day cycle.
Drug: Bevacizumab
IV infusion
Drug: Onvansertib
Oral capsule
Drug: FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
Active Comparator: Standard of Care (SOC)
Participants will receive SOC (FOLFIRI + bevacizumab) on Days 1 and 15 of each 28-day cycle.
Drug: Bevacizumab
IV infusion
Drug: FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) 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
Overall Response Rate
Time Frame: Up to approximately 1 year
Defined as complete response (CR) or partial response (PR) as determined according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by an 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
Maximum Concentration (Cmax) of Onvansertib
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
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
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)
Maximum Concentration (Cmax) of Onvansertib Metabolites
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 Metabolites
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 Metabolites
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)
Progression-free Survival (PFS)
Time Frame: Up to approximately 1 year
Defined from the date of first drug administration to progression or death, whichever occurs first.
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), physical examinations, 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
Defined as CR plus PR plus stable disease (SD).
Up to approximately 1 year
Duration of Response (DOR)
Time Frame: Up to approximately 1 year
Defined from the date of first response (CR or PR) to disease progression (PD) or death, whichever occurs first.
Up to approximately 1 year
Overall Survival (OS)
Time Frame: Up to approximately 1 year
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 mutation allele frequency (MAF).
Up to approximately 1 year
Efficacy: Exposure Response Evaluation of Onvansertib
Time Frame: Up to approximately 1 year
Correlation between onvansertib exposure and overall response rate.
Up to approximately 1 year
Safety: Exposure Response Evaluation of Onvansertib
Time Frame: Up to approximately 1 year
Correlation between onvansertib exposure and the number of participants with an AE.
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

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.
March 17, 2023

Primary Completion (Actual)

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.
December 9, 2024

Study Completion (Actual)

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.
December 9, 2024

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 20, 2022

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 20, 2022

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 25, 2022

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.
March 25, 2025

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.
January 9, 2025

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.
January 1, 2025

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-003

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

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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