Study of Onvansertib in Combination With FOLFIRI and Bevacizumab Versus FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Participants With a Kirsten Rat Sarcoma Virus Gene (KRAS) or Neuroblastoma-RAS (NRAS) Mutation

NCT05593328 | Completed Phase 2 FDA Drug

• 1 other identifier: CRDF-003
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 27

Brief Summary

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.

Conditions

Colorectal Cancer; Metastatic Colorectal Cancer

Keywords

Colorectal Cancer; Metastatic Colorectal Cancer; KRAS Mutation; NRAS Mutation; Onvansertib; FOLFIRI; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to approximately 1 year

Secondary Outcomes (14)

• Progression-free Survival (PFS)

  Up to approximately 1 year

• Number of Participants with an Adverse Event (AE)

  Up to approximately 1 year

• Disease Control Rate (DCR)

  Up to approximately 1 year

• Duration of Response (DOR)

  Up to approximately 1 year

• Overall Survival (OS)

  Up to approximately 1 year

Study Arms (3)

Onvansertib 20 mg + Standard of Care (SOC)

EXPERIMENTAL

Participants will receive 20 mg of onvansertib on Days 1 to 5 and 15 to 19 of a 28-day treatment cycle and SOC (FOLFIRI + bevacizumab) on Days 1 and 15 of each 28-day cycle.

Drug: Onvansertib; Drug: FOLFIRI; Drug: Bevacizumab

Onvansertib 30 mg + Standard of Care (SOC)

EXPERIMENTAL

Participants will receive 30 mg of onvansertib on Days 1 to 5 and 15 to 19 of a 28-day treatment cycle and SOC (FOLFIRI + bevacizumab) on Days 1 and 15 of each 28-day cycle.

Drug: Onvansertib; Drug: FOLFIRI; Drug: Bevacizumab

Standard of Care (SOC)

ACTIVE COMPARATOR

Participants will receive SOC (FOLFIRI + bevacizumab) on Days 1 and 15 of each 28-day cycle.

Drug: FOLFIRI; Drug: Bevacizumab

Interventions

Onvansertib DRUG

Oral capsule

Onvansertib 20 mg + Standard of Care (SOC); Onvansertib 30 mg + Standard of Care (SOC)

FOLFIRI DRUG

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

Onvansertib 20 mg + Standard of Care (SOC); Onvansertib 30 mg + Standard of Care (SOC); Standard of Care (SOC)

Bevacizumab DRUG

IV infusion

Onvansertib 20 mg + Standard of Care (SOC); Onvansertib 30 mg + Standard of Care (SOC); Standard of Care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic and/or unresectable colorectal cancer (CRC).
• Documentation of a kirsten rat sarcoma virus gene (KRAS) or neuroblastoma-RAS (NRAS) mutation in exon 2, 3, or 4 in primary tumor or metastasis, assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
• Age ≥ 18 years.
• Participants with tumors that have progressed on an oxaliplatin/fluoropyrimidine--based regimen with or without bevacizumab.
• Participants must have had systemic therapy within 180 days of the screening visit.
• Participants must have, at any time previously, received oxaliplatin-based chemotherapy with or without bevacizumab (≥ 6 weeks in duration).
• Participants who received oxaliplatin/fluoropyrimidine-based neoadjuvant, adjuvant, and/or fluoropyrimidine maintenance or adjuvant therapy and have disease recurrence or progression \> 6 months from their last dose of oxaliplatin will be required to have received oxaliplatin/fluoropyrimidine-based therapy with or without bevacizumab as first-line treatment for metastatic disease.
• Participants who received an oxaliplatin-based regimen in the first-line setting and discontinued oxaliplatin because of toxicity or who received oxaliplatin for maintenance therapy are eligible as long as progression occurred \< 6 months after the last dose of oxaliplatin therapy for advanced metastatic disease. It is recommended that these participants be re-challenged (if feasible) with oxaliplatin/fluoropyrimidine therapy and subsequently progress prior to eligibility. Participants with oxaliplatin-related neuropathy or oxaliplatin infusion-related hypersensitivity that cannot be rechallenged with oxaliplatin are eligible.
• Participants must not have received prior treatment with irinotecan.
• FOLFIRI therapy is appropriate for the participant as determined by the Investigator.
• Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib. Only participants with measurable disease as defined per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) are eligible for enrollment. CT is the preferred imaging modality, but MRI is also accepted. All subsequent scans must consistently use the same imaging modality for comparison with the Screening scan throughout the study.
• Must have acceptable organ function
• Signed informed consent to provide blood sample(s) for specific correlative assays

You may not qualify if:

• Concomitant KRAS or NRAS and BRAF-V600 mutation or Microsatellite Instability High/Deficient Mismatch Repair (MSI-H/dMMR).
• Anti-cancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug. The exception is a single dose of radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before enrollment, provided it is not the target lesion.
• More than 1 prior chemotherapy regimen administered in the metastatic setting.
• Major surgery within 6 weeks prior to enrollment.
• Untreated or symptomatic brain metastasis.
• Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would significantly impede the absorption of an oral agent (e.g., intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
• Unable or unwilling to swallow study drug.
• Known hypersensitivity to fluoropyrimidine or leucovorin.
• Known hypersensitivity to irinotecan.
• Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
• QT interval:
• Fridericia's correction (QTcF) \> 470 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate electrocardiograms (ECGs). In the case of potentially correctible causes of QT prolongation that are readily corrected (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during Screening and that result may be used to determine eligibility.
• Planned concomitant use of medications known to prolong the QT/QTc interval according to institutional guidelines.
• Presence of risk factors for torsade de pointes, including family history of Long QT Syndrome or uncorrected hypokalemia.
• Use of strong cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C19 (CYP2C19) inhibitors or strong CYP3A4 inducers. Participants currently receiving these agents who can be switched to alternate therapy are not excluded. Inhibitors should be stopped at least 1 week prior to the first dose of protocol therapy and inducers should be stopped at least 2 weeks prior to initiation of protocol therapy.

Sponsors & Collaborators

• Cardiff Oncology: lead

Study Sites (27)

Mayo Clinic in Arizona - Phoenix Campus

Phoenix, Arizona, 85054, United States

Location

Central Arkansas Radiation Therapy Institute - Cancer Center

Little Rock, Arkansas, 72205-6523, United States

Location

Pacific Cancer Medical Center

Anaheim, California, 92801, United States

Location

Comprehensive Blood and Cancer Center - Bakersfield

Bakersfield, California, 93309, United States

Location

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

Location

Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCI Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

UCLA Health - Santa Monica Parkside Cancer Care

Santa Monica, California, 90404, United States

Location

Torrance Memorial Physician Network - Cancer Care and Infusion Center

Torrance, California, 90505, United States

Location

PIH Health

Whittier, California, 90602, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

Location

Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine Center for Advanced Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists - Midwest Cancer Center - Legacy

Omaha, Nebraska, 68130, United States

Location

Englewood Health

Englewood, New Jersey, 07631, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Manhattan Hematology Oncology Associates

New York, New York, 10016, United States

Location

Gabrail Cancer and Research Center

Canton, Ohio, 44718, United States

Location

Trihealth Kenwood

Cincinnati, Ohio, 45236, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

West Cancer Center - East Campus

Germantown, Tennessee, 38138, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22903, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

onvansertib; IFL protocol; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2022
• First Posted: October 25, 2022
• Study Start: March 17, 2023
• Primary Completion: December 9, 2024
• Study Completion: December 9, 2024
• Last Updated: January 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (27)