Onvansertib + Chemotherapy for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
+40 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Cardiff Oncology
Must not be taking: Strong CYP3A4 inhibitors
Disqualifiers: BRAF-V600 mutation, Brain metastasis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but you cannot use strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers. It's best to discuss your current medications with the trial team.
What makes the drug Onvansertib unique for colorectal cancer treatment?
Onvansertib is unique because it is a targeted therapy that works by inhibiting a specific enzyme called PLK1, which is involved in cancer cell division. This mechanism is different from traditional chemotherapy, which generally targets all rapidly dividing cells.
12345Eligibility Criteria
This trial is for adults with metastatic colorectal cancer that has specific mutations (KRAS or NRAS). They should not have had previous systemic therapy for their metastatic condition, must be able to undergo scans to document the disease, and agree to provide tissue samples. Participants need to be relatively active and healthy (ECOG status 0 or 1) and take steps to prevent pregnancy.Inclusion Criteria
Participants must be willing to submit archival tissue or undergo fresh biopsy
Women of childbearing potential must use contraception or take measures to avoid pregnancy
My colorectal cancer has spread and was confirmed by a lab test.
+5 more
Exclusion Criteria
I have a known DPD deficiency.
I have been treated with oxaliplatin in the last 12 months.
Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxaliplatin
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive onvansertib in combination with FOLFIRI and bevacizumab or FOLFOX and bevacizumab in 28-day cycles
Up to approximately 1 year
Visits on Day 1 and Day 15 of each 28-day cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Participant Groups
The study is testing two different doses of a drug called Onvansertib in combination with standard chemotherapy regimens FOLFIRI or FOLFOX, both also paired with Bevacizumab. The goal is to find the lowest effective dose of Onvansertib and evaluate its safety and effectiveness against metastatic colorectal cancer.
6Treatment groups
Experimental Treatment
Active Control
Group I: Onvansertib 30 mg + Standard of Care (SOC)Experimental Treatment3 Interventions
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.
Group II: Onvansertib 30 mg + Standard of CareExperimental Treatment3 Interventions
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.
Group III: Onvansertib 20mg + Standard of CareExperimental Treatment3 Interventions
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.
Group IV: Onvansertib 20 mg + Standard of CareExperimental Treatment3 Interventions
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.
Group V: Standard of CareActive Control2 Interventions
Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
Group VI: Standard of Care (SOC)Active Control2 Interventions
Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.
Onvansertib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Onvansertib for:
- Acute Myeloid Leukemia (AML) - Orphan Drug Designation
🇪🇺 Approved in European Union as Onvansertib for:
- Acute Myeloid Leukemia (AML) - Orphan Drug Designation
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Torrance Memorial Physician Network - Cancer Care and Infusion CenterTorrance, CA
PIH HealthWhittier, CA
Mayo Clinic Cancer CenterRochester, MN
St. Bernards Medical CenterJonesboro, AR
More Trial Locations
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Who Is Running the Clinical Trial?
Cardiff OncologyLead Sponsor
PfizerIndustry Sponsor
References
Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial. [2023]Microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and anti-angiogenesis therapy have been reported to potentially promote immunotherapy response. This study aims to assess the preliminary anti-tumor activity and safety of sintilimab plus bevacizumab, oxaliplatin and capecitabine as a treatment option for patients with RAS-mutant MSS mCRC.
A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer. [2022]FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine.
Preliminary Efficacy and Safety of Camrelizumab in Combination With XELOX Plus Bevacizumab or Regorafenib in Patients With Metastatic Colorectal Cancer: A Retrospective Study. [2022]For a majority of patients with metastatic colorectal cancer (mCRC) with MS stable (MSS) or mismatch repair proficient (pMMR), the role of immunotherapy is undetermined. This study investigated the efficacy and safety of camrelizumab when added to XELOX chemotherapy plus bevacizumab or regorafenib as first-line therapy for mCRC.
Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup Trial N9741. [2018]Intergroup Trial N9741 evaluated 5-fluorouracil (5-FU)/leucovorin (LV) administered in conjunction with either irinotecan or oxaliplatin in the first-line treatment of advanced colorectal carcinoma (CRC). The current report describes two treatment arms that were withdrawn from the protocol due to unexpected treatment-related toxicities and a high mortality rate. The complications observed in these arms highlight the importance of aggressive and immediate supportive care in the management of digestive toxicity.
Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. [2022]Cotargeting vascular endothelial growth factor and programmed cell death 1 or programmed cell death ligand 1 may produce anticancer activity in refractory metastatic colorectal cancer (mCRC). The clinical benefit of atezolizumab combined with chemotherapy and bevacizumab remains unclear for the treatment of mCRC.