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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06106308
• Other study ID #: CRDF-004
• Status: Recruiting
• Phase: Phase 2
• Start date: February 27, 2024
• Est. completion date: January 2027

Study information

• Verified date: May 2024
• Source: Cardiff Oncology
• Contact: Nancy Sherman
• Phone: 858-952-7570
• Email: patients[@]cardiffoncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• CRC
• Metastatic Colorectal Cancer

Intervention

Drug:
• Onvansertib
Oral capsule
• FOLFIRI
FOLFIRI (irinotecan + fluorouracil [5-FU] + leucovorin) as intravenous (IV) infusion
• Bevacizumab
IV Infusion
• FOLFOX
FOLFOX (leucovorin + fluorouracil [5-FU] + oxaliplatin) as intravenous (IV) infusion

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Comprehensive Blood and Cancer Center - Bakersfield	Bakersfield	California
United States	University of Virginia	Charlottesville	Virginia
United States	Trihealth Kenwood	Cincinnati	Ohio
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	West Cancer Clinic	Germantown	Tennessee
United States	Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion	Grand Rapids	Michigan
United States	Memorial Cancer Institute	Hollywood	Florida
United States	Kaiser Permanente	Honolulu	Hawaii
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic - Florida	Jacksonville	Florida
United States	St. Bernards Medical Center	Jonesboro	Arkansas
United States	CCCN	Las Vegas	Nevada
United States	Norris Comprehensive Cancer Center	Los Angeles	California
United States	Manhattan Hematology Oncology (MHO) Research Foundation, Inc.	New York	New York
United States	Mayo Clinic - Arizona	Phoenix	Arizona
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Washington University School of Medicine Center for Advanced Medicine	Saint Louis	Missouri
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Torrance Memorial Physician Network - Cancer Care and Infusion Center	Torrance	California
United States	The University of Kansas Cancer Center - Westwood	Westwood	Kansas
United States	PIH Health	Whittier	California
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Cardiff Oncology	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	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.	Up to approximately 1 year
Secondary	Progression Free Survival (PFS)	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.	Up to approximately 1 year
Secondary	Duration of Response (DOR)	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.	Up to approximately 1 year
Secondary	Number of Participants with an Adverse Event (AE)	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.	Up to approximately 1 year
Secondary	Disease Control Rate (DCR)	DCR defined as CR plus PR plus stable disease (SD), as determined by independent central review.	Up to approximately 1 year
Secondary	Overall Survival (OS)	OS defined as the time from drug administration to death due to any cause.	Up to approximately 1 year
Secondary	Overall Response (OR)	Defined as CR or PR, PFS, DCR, DOR, and OS associated with a reduction in circulating tumor DNA (ctDNA) mutation allele frequency (MAF).	Up to approximately 1 year
Secondary	Maximum Concentration (Cmax) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab		Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Secondary	Area Under the Plasma Concentration Curve (AUC) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab		Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Secondary	Trough Concentration (Ctrough) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab		Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Secondary	Efficacy: Exposure Response Evaluation of Onvansertib		Up to approximately 1 year
Secondary	Safety: Exposure Response Evaluation of Onvansertib		Up to approximately 1 year