Open Actively Recruiting

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

About

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

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