Actively Recruiting
Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer
Led by National Cancer Institute (NCI) · Updated on 2026-06-03
24
Participants Needed
13
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the side effects and best dose of CA-4948 (emavusertib) combined with chemotherapy drugs FOLFOX (fluorouracil, leucovorin, and oxaliplatin) plus bevacizumab in patients with metastatic colorectal cancer. This phase I trial aims to find a safe and tolerable dose while assessing the impact on tumor growth and signaling pathways. The study also explores biomarkers and gene mutations related to treatment response and survival outcomes. Participants receive CA-4948 orally twice daily for 14 days in each 14-day cycle, along with intravenous bevacizumab, oxaliplatin, leucovorin, and fluorouracil according to two treatment groups that differ in the timing of bevacizumab administration. Treatment cycles continue for up to two years, unless disease progression or unacceptable side effects occur. Patients may continue treatment beyond two years after discussion with the study chair. During the trial, patients undergo blood sample collection, imaging scans (CT, MRI, PET/CT), and tumor biopsies. Participants are monitored closely for side effects and dose-limiting toxicities during the first two cycles. Safety and anti-tumor activity are assessed throughout treatment and up to 12 months after. Follow-up visits occur 30 days after treatment ends and then every three months for one year. The study collects molecular profiling data at multiple points to evaluate treatment effects. Overall survival, progression-free survival, and disease control rates are key outcomes being measured.
CONDITIONS
Brief Title
Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must have confirmed colorectal adenocarcinoma
- Must have unresectable or metastatic measurable disease on imaging within 28 days before registration
- Lesions must be suitable for research biopsy for expansion cohort patients
- Age 18 years or older
- ECOG performance status 0 to 2 or Karnofsky 60% or higher
- Absolute neutrophil count 1,500/mcL or higher within 28 days before registration
- Platelet count 75,000/mcL or higher within 28 days before registration
- Total bilirubin less than or equal to 1.5 times the institutional upper limit of normal (ULN) within 28 days before registration
- AST/ALT less than or equal to 3 times ULN, or 5 times ULN if liver metastases present, within 28 days before registration
- Estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 m2 or higher within 28 days before registration
- Creatine phosphokinase elevation less than grade 2 within 28 days before registration
- Stable dose of cholesterol-lowering statins for at least 3 weeks before study start
- HIV-infected patients on effective therapy with undetectable viral load within 6 months
- Patients with chronic hepatitis B must have undetectable viral load if on therapy
- Patients with treated or cured hepatitis C infection, or undetectable viral load if on treatment
- Patients with treated brain metastases showing no progression on follow-up imaging
- Patients with active brain metastases may be eligible after discussion if no immediate CNS treatment is needed
- Patients with prior or concurrent malignancies not interfering with study safety or efficacy
- Cardiac function classified as New York Heart Association class II or better
- Ability to take oral medications
- Women and men of childbearing potential must agree to use contraception during and after study participation
- Ability and willingness to provide informed consent or have a legally authorized representative consent
You will not qualify if you...
- Patients with high-frequency microsatellite instability (MSI-H) or deficient DNA mismatch repair (dMMR) colorectal cancer
- Prolonged QT interval over 450ms on screening ECG
- Unresolved adverse events greater than grade 1 from prior cancer therapy except alopecia
- Use of any other investigational agents
- Prior chemotherapy including FOLFOX, FOLFIRI, FOLFOXIRI, or antiangiogenic agents like bevacizumab
- Known dihydropyrimidine dehydrogenase deficiency
- Allergic reactions to CA-4948 or similar agents
- Gastrointestinal conditions impairing CA-4948 absorption or ingestion
- Uncontrolled illnesses or conditions making participation hazardous
- Pregnant or breastfeeding women; negative pregnancy test required for women of childbearing potential
- History of allogeneic organ or stem cell transplantation
- Significant active bleeding or safety concerns for bevacizumab use
- Recent palliative radiation to bone metastases within 2 weeks prior to study
- Major surgery within 4 weeks prior to study
- Uncontrolled hypertension
- Recent systemic immunosuppressive treatment within 14 days before randomization except low-dose corticosteroids
- Severe infections within 28 days prior to registration including recent antibiotic use except prophylactic antibiotics
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 years
Participants receive CA-4948 orally twice daily on days 1-14 of each 14-day cycle, combined with chemotherapy drugs oxaliplatin, leucovorin, and fluorouracil given intravenously on day 1 of each cycle. Bevacizumab is given intravenously on day 1 of each cycle starting in cycle 1 for Group A participants and starting in cycle 2 for Group B participants. Treatment cycles repeat every 14 days for up to 2 years unless disease progresses or unacceptable side effects occur. Participants undergo blood sample collection and imaging scans throughout treatment and may undergo tumor biopsies.
Every 14 days for treatment cycles with additional imaging and blood sample visits throughout treatment
Duration - Up to 12 months
After completing treatment, participants are followed up at 30 days and then every 3 months for up to 12 months to monitor their health and disease status.
1 visit at 30 days post-treatment and then visits every 3 months
Trial Site Locations
Total: 13 locations
1
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States, 32610
Actively Recruiting
2
Memorial Hospital East
Shiloh, Illinois, United States, 62269
Actively Recruiting
3
University of Kansas Clinical Research Center
Fairway, Kansas, United States, 66205
Actively Recruiting
4
University of Kansas Cancer Center
Kansas City, Kansas, United States, 66160
Actively Recruiting
5
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States, 66211
Actively Recruiting
6
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States, 66205
Actively Recruiting
7
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States, 63376
Actively Recruiting
8
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States, 63141
Actively Recruiting
9
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
10
Siteman Cancer Center-South County
St Louis, Missouri, United States, 63129
Actively Recruiting
11
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States, 63136
Actively Recruiting
12
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Actively Recruiting
13
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here