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

Purpose

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.

Conditions

  • Metastatic Colorectal Cancer
  • CRC
  • KRAS/NRAS Mutation

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

The University of Kansas Cancer Center - Westwood
Westwood, Kansas 66205
Contact:
Study Coordinator
913-588-1227

More Details

Status
Recruiting
Sponsor
Cardiff Oncology

Study Contact

Nancy Sherman
858-952-7570
patients@cardiffoncology.com