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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

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ClinicalTrials.gov Identifier: NCT06106308
Recruitment Status : Recruiting
First Posted : October 30, 2023
Last Update Posted : May 3, 2024
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Cardiff Oncology

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer CRC KRAS/NRAS Mutation Drug: Onvansertib Drug: FOLFIRI Drug: Bevacizumab Drug: FOLFOX Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 27, 2024
Estimated Primary Completion Date : November 2026
Estimated Study Completion Date : January 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Overall Survival (OS) [ Time Frame: Up to approximately 1 year ]
    OS defined as the time from drug administration to death due to any cause.

  6. 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).

  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. Efficacy: Exposure Response Evaluation of Onvansertib [ Time Frame: Up to approximately 1 year ]
  11. Safety: Exposure Response Evaluation of Onvansertib [ Time Frame: Up to approximately 1 year ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • 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
Contacts and Locations
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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): NCT06106308


Contacts
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Contact: Nancy Sherman 858-952-7570 patients@cardiffoncology.com

Locations
Show Show 24 study locations
Sponsors and Collaborators
Cardiff Oncology
Pfizer
More Information
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Responsible Party: Cardiff Oncology
ClinicalTrials.gov Identifier: NCT06106308    
Other Study ID Numbers: CRDF-004
First Posted: October 30, 2023    Key Record Dates
Last Update Posted: May 3, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cardiff Oncology:
Metastatic Colorectal Cancer
KRAS Mutation
NRAS Mutation
CRC
First-Line
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
 Onvansertib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action