University of Kansas Medical Center

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

Arm	Description	Assigned 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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.