Active, not recruitingNCT06106308ClinicalTrials.gov record

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 · CRC · KRAS/NRAS Mutation

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THE QUICK READ

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type: Interventional
Phase: Phase 2
Age range: 18 years - Not specified
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 110 Actual

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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

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Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: No masking

Onvansertib 20mg + Standard of Care

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.

Drug: Onvansertib · Drug: FOLFIRI · Drug: Bevacizumab

Onvansertib 30 mg + Standard of Care (SOC)

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.

Drug: Onvansertib · Drug: FOLFIRI · Drug: Bevacizumab

Standard of Care (SOC)

Participants will receive FOLFIRI/Bev on Day 1 and Day 15 of each 28-day treatment cycle.

Drug: FOLFIRI · Drug: Bevacizumab

Onvansertib 20 mg + Standard of Care

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.

Drug: Onvansertib · Drug: Bevacizumab · Drug: FOLFOX

Onvansertib 30 mg + Standard of Care

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.

Drug: Onvansertib · Drug: Bevacizumab · Drug: FOLFOX

Standard of Care

Participants will receive FOLFOX/Bev on Day 1 and Day 15 of each 28-day treatment cycle.

Drug: Bevacizumab · Drug: FOLFOX

Onvansertib DRUG

Oral capsule

FOLFIRI DRUG

FOLFIRI (irinotecan + fluorouracil \[5-FU\] + leucovorin) as intravenous (IV) infusion

Bevacizumab DRUG

IV Infusion

FOLFOX DRUG

FOLFOX (leucovorin + fluorouracil \[5-FU\] + oxaliplatin) as intravenous (IV) infusion

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Objective Response Rate (ORR)

Time frame: Up to approximately 1 year

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.

Secondary measures

Progression Free Survival (PFS)

Time frame: Up to approximately 1 year

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.

Duration of Response (DOR)

Time frame: Up to approximately 1 year

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.

Number of Participants with an Adverse Event (AE)

Time frame: Up to approximately 1 year

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.

Disease Control Rate (DCR)

Time frame: Up to approximately 1 year

DCR defined as CR plus PR plus stable disease (SD), as determined by independent central review.

Overall Survival (OS)

Time frame: Up to approximately 1 year

OS defined as the time from drug administration to death due to any cause.

Overall Response (OR)

Time frame: Up to approximately 1 year

Defined as CR or PR, PFS, DCR, DOR, and OS associated with a reduction in circulating tumor DNA (ctDNA) mutation allele frequency (MAF).

Maximum Concentration (Cmax) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab

Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)

Not reported in this registry record.

Area Under the Plasma Concentration Curve (AUC) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab

Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)

Not reported in this registry record.

Trough Concentration (Ctrough) of Onvansertib and metabolites in combination w/FOLFIRI and bevacizumab or FOLFOX and bevacizumab

Time frame: Day 1 and Day 5 of Cycle 1, and Day 5 of Cycle 3 (cycle is 28 days)

Not reported in this registry record.

Efficacy: Exposure Response Evaluation of Onvansertib

Time frame: Up to approximately 1 year

Not reported in this registry record.

Safety: Exposure Response Evaluation of Onvansertib

Time frame: Up to approximately 1 year

Not reported in this registry record.

No results are flagged as posted.

Review the complete result tables and limitations in the official record.

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Research locations (41)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

Find a location in this study

41 locations

Mayo Clinic - ArizonaPhoenix, Arizona, United StatesStatus unknown

What this study involves

About the research

Who may be able to participate?

Treatment, groups and participation

What researchers are measuring

Primary measures

Secondary measures

Research locations (41)

Study team and timeline

Official study contacts

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