The primary objective of this study is to assess the efficacy of 2 different doses of onvansertib in combination with a chemotherapy regimen of irinotecan, fluorouracil \[5-FU\], and leucovorin (FOLFIRI) and bevacizumab for treatment of confirmed metastatic and/or unresectable colorectal cancer (CRC) in participants with a kirsten rat sarcoma virus gene (KRAS) or neuroblastoma-RAS (NRAS) mutation who have progressed on an oxaliplatin/fluoropyrimidinebased regimen in the first-line setting.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Oral capsule
FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion
IV infusion
Mayo Clinic in Arizona - Phoenix Campus
Phoenix, Arizona, United States
Central Arkansas Radiation Therapy Institute - Cancer Center
Little Rock, Arkansas, United States
Pacific Cancer Medical Center
Anaheim, California, United States
Comprehensive Blood and Cancer Center - Bakersfield
Bakersfield, California, United States
Cancer and Blood Specialty Clinic
Los Alamitos, California, United States
Overall Response Rate
Defined as complete response (CR) or partial response (PR) as determined according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by an independent central review.
Time frame: Up to approximately 1 year
Progression-free Survival (PFS)
Defined from the date of first drug administration to progression or death, whichever occurs first.
Time frame: Up to approximately 1 year
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), physical examinations, weight, and Eastern Cooperative Oncology Group (ECOG) performance status will be recorded as AEs.
Time frame: Up to approximately 1 year
Disease Control Rate (DCR)
Defined as CR plus PR plus stable disease (SD).
Time frame: Up to approximately 1 year
Duration of Response (DOR)
Defined from the date of first response (CR or PR) to disease progression (PD) or death, whichever occurs first.
Time frame: Up to approximately 1 year
Overall Survival (OS)
Defined as the time from drug administration to death due to any cause.
Time frame: Up to approximately 1 year
Overall Response (OR)
Defined as CR or PR, PFS, DCR, DOR, and OS associated with a reduction in mutation allele frequency (MAF).
Time frame: Up to approximately 1 year
Maximum Concentration (Cmax) of Onvansertib
Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Area Under The Plasma Concentration Curve (AUC) of Onvansertib
Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Trough Concentration (Ctrough) of Onvansertib
Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Maximum Concentration (Cmax) of Onvansertib Metabolites
Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Area Under The Plasma Concentration Curve (AUC) of Onvansertib Metabolites
Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Trough Concentration (Ctrough) of Onvansertib Metabolites
Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)
Efficacy: Exposure Response Evaluation of Onvansertib
Correlation between onvansertib exposure and overall response rate.
Time frame: Up to approximately 1 year
Safety: Exposure Response Evaluation of Onvansertib
Correlation between onvansertib exposure and the number of participants with an AE.
Time frame: Up to approximately 1 year
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Norris Comprehensive Cancer Center
Los Angeles, California, United States
UCI Health - Chao Family Comprehensive Cancer Center
Orange, California, United States
UCLA Health - Santa Monica Parkside Cancer Care
Santa Monica, California, United States
Torrance Memorial Physician Network - Cancer Care and Infusion Center
Torrance, California, United States
PIH Health
Whittier, California, United States
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