Clinical trial NCT06106308: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
CRC
KRAS/NRAS Mutation
Keywords: Metastatic Colorectal Cancer
KRAS Mutation
NRAS Mutation
CRC
First-Line
Lead sponsor: Cardiff Oncology
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2023-10-30
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 1 year
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 1 year
measure: Duration of Response (DOR)
timeFrame: Up to approximately 1 year
measure: Number of Participants with an Adverse Event (AE)
timeFrame: Up to approximately 1 year
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 1 year
measure: Overall Survival (OS)
timeFrame: Up to approximately 1 year
measure: Overall Response (OR)
timeFrame: Up to approximately 1 year
measure: Maximum Concentration (Cmax) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab
timeFrame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
measure: Area Under the Plasma Concentration Curve (AUC) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab
timeFrame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
measure: Trough Concentration (Ctrough) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab
timeFrame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
measure: Efficacy: Exposure Response Evaluation of Onvansertib
timeFrame: Up to approximately 1 year
measure: Safety: Exposure Response Evaluation of Onvansertib
timeFrame: Up to approximately 1 year
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Jonesboro
country: United States
facility: St. Bernards Medical Center
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center - Bakersfield
state: California
city: Fountain Valley
country: United States
facility: Orange Coast Memorial Medical Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine-Hematology/Oncology
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Torrance
country: United States
facility: Torrance Memorial Physician Network - Cancer Care and Infusion Center
state: California
city: Whittier
country: United States
facility: PIH Health
state: California
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Florida
state: Florida
city: Stuart
country: United States
facility: Cleveland Clinic Martin Health
state: Florida
city: Honolulu
country: United States
facility: Kaiser Permanente
state: Hawaii
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Westwood
country: United States
facility: The University of Kansas Cancer Center - Westwood
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine Center for Advanced Medicine
state: Missouri
city: Las Vegas
country: United States
facility: CCCN
state: Nevada
city: New York
country: United States
facility: Manhattan Hematology Oncology (MHO) Research Foundation, Inc.
state: New York
city: Cincinnati
country: United States
facility: Trihealth Kenwood
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Clinic
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants, PA
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center
state: Wisconsin
Study officials:
References: