Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer
Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer
3 other identifiers
interventional
24
1 country
13
Brief Summary
This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLFOX, fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jun 2025
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 19, 2024
CompletedFirst Posted
Study publicly available on registry
November 20, 2024
CompletedStudy Start
First participant enrolled
June 23, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
April 13, 2026
February 1, 2026
1.5 years
November 19, 2024
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Dose limiting toxicities (DLT)
DLT will be based on the first 2 cycles (28 days) of emavusertib.
Up to 2 cycles (Cycle length = 14 days)
Incidence of treatment-emergent adverse events
The adverse events will be recorded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Up to 2 cycles (Cycle length = 14 days)
Secondary Outcomes (6)
Incidence of adverse events
Baseline to 30 days after last dose of study drug
Overall response rate
From the start of treatment until disease progression/recurrence, assessed up to 12 months after end of treatment
Progression free survival
From first dose to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed up to 12 months after end of treatment
Overall survival
From the date of first dose to the date of death by any cause, assessed up to 12 months after end of treatment
Disease control rate
Up to 12 months after end of treatment
- +1 more secondary outcomes
Other Outcomes (5)
Pharmacodynamic (PD) biomarkers
At baseline, between C1D10 and C1D14, and disease progression
Pharmacokinetic (PK) parameters
C1D1, 0.5, 1, 2, 4, 6, and 8 hours post-dose on C2D1, C3D1
Immune profiling
At baseline, day 1 of each cycle, and 30 days after last dose of study drug
- +2 more other outcomes
Study Arms (2)
Group A (CA-4948, bevacizumab, FOLFOX)
EXPERIMENTALPatients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 1, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients may also undergo tumor biopsy throughout the trial.
Group B (CA-4948, bevacizumab, FOLFOX)
EXPERIMENTALPatients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 2, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients also undergo tumor biopsy throughout the trial.
Interventions
Undergo blood sample collection
Given PO
Given IV
Given IV
Undergo MRI
Given IV
Undergo PET/CT
Undergo tumor biopsy
Undergo CT or PET/CT
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed colorectal adenocarcinoma
- Patients must have unresectable or metastatic measurable disease on imaging for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 determination within 28 days of registration
- For patients enrolling to the expansion cohort, lesions must be amenable to research biopsy
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CA-4948 (emavusertib) and FOLFOX in combination with bevacizumab in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
- Absolute neutrophil count ≥ 1,500/mcL (within 28 days of registration)
- Platelets ≥ 75,000/mcL (within 28 days of registration)
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (within 28 days of registration)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN; for those with liver metastases, 5 × institutional ULN (within 28 days of registration)
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 (within 28 days of registration)
- Creatine phosphokinase (CPK) elevation at screening \< grade 2 (CPK ≤ 2.5 x ULN) (within 28 days of registration)
- Patients on a cholesterol lowering statin must be on a stable dose with no dose changes within 3 weeks prior to study start
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- +7 more criteria
You may not qualify if:
- Patients with high-frequency microsatellite instability (MSI-H) or deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) colorectal cancer at pre-enrollment screening
- Patients with prolonged QT interval by Fridericia's correction formula (QTcF) (\> 450ms) on screening electrocardiogram (ECG)
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients who have received prior treatment with any chemotherapy (either in the adjuvant or metastatic setting), including FOLFOX, fluorouracil/leucovorin/irinotecan (FOLFIRI), folinic acid/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI), or antiangiogenic agents such as bevacizumab and similar agents, are not eligible for this study
- Patients with a known dihydropyrimidine dehydrogenase deficiency
- Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948 (emavusertib) or other agents used in the study
- Patients with a gastrointestinal (GI) condition that could impair absorption of CA-4948 (emavusertib) or cause an inability to ingest CA-4948 (emavusertib)
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because CA-4948 (emavusertib) is a blood-brain barrier penetrant with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CA-4948 (emavusertib), breastfeeding should be discontinued if the mother is treated with CA-4948 (emavusertib). These potential risks may also apply to other agents used in this study. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry
- Patients with a history of allogeneic organ or stem cell transplantation
- Patients with significant active bleeding or those in whom the treating physician believes bevacizumab would not be safe or appropriate
- Patients who have had palliative radiation to bone metastases within 2 weeks prior to day 1 of the study treatment
- Patients who have had a major surgical procedure within 4 weeks prior to day 1 of the study treatment
- Patients with hypertension not controlled by antihypertensive medication
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Susanna V Ulahannan
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 19, 2024
First Posted
November 20, 2024
Study Start
June 23, 2025
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
April 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.