EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer
A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer
1 other identifier
interventional
2
1 country
1
Brief Summary
The purpose of this study is to determine the immunogenicity of the CIMAvaxEGF® vaccine (that is, its effectiveness in inducing an anti-tumor immune response) in patients with metastatic KRAS/NRAS/BRAF wild-type gene colorectal cancer, when given in combination with standard therapies used in the treatment of advanced colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for early_phase_1 colorectal-cancer
Started Dec 2023
Typical duration for early_phase_1 colorectal-cancer
1 active site
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
August 21, 2023
CompletedFirst Posted
Study publicly available on registry
August 25, 2023
CompletedStudy Start
First participant enrolled
December 18, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 5, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
December 4, 2026
ExpectedMarch 11, 2026
March 1, 2026
2.1 years
August 21, 2023
March 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Immunogencity of vaccine
Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method
up to 60 days after last dose
Secondary Outcomes (1)
Progression free survival
time from treatment until disease progression, death or last follow up assesed up to 2 years
Study Arms (3)
Cohort A
EXPERIMENTALLOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.
Cohort B
EXPERIMENTALLOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial.
Cohort C
EXPERIMENTALDescription LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial.
Interventions
Given IM
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed \>12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed \<12 months from diagnosis of metastatic or advanced disease is considered one line of therapy).
- Cohort A: May have received 1 cycle of chemotherapy± appropriate biologic agent pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will receive the addition of CIMAvax + Bevacizumab or CIMAvax+ anti-EGFR therapy in their second cycle.
- Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease
- Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for metastatic disease resistant resection (one cycle of standard chemotherapy with or without appropriate biologic agent is allowed)
- KRAS/NRAS/BRAF wild-type.
- Have an ECOG Performance Status of 0-2
- Patients must have adequate organ and marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 75 x 10\^9/L
- Hemoglobin ≥ 8 g/dL
- Creatinine clearance\> 60 mL/min (Cockcroft-Gault Equation)
- ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present
- Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range
- Have measurable disease per RECIST 1.1 criteria present.
- Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- +2 more criteria
You may not qualify if:
- Toxicity ≥Grade 2 from prior chemotherapy with exception to Grade 2 peripheral neuropathy..
- Other cancer requiring active treatment.
- Participants with Her2 positive mutational status
- Had major surgery within 4 weeks prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.
- Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing disease). Testing is not mandatory.
- Participants with known active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
- Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease
- History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline
- Uncontrolled hypertension (SBP\>160/DBP\>100 despite medical intervention).
- History of myocarditis of any etiology
- History of ventricular arrhythmias
- Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition.
- Pregnant or nursing female participants.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anuradha Krishnamurthy, MBBS
Roswell Park Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 21, 2023
First Posted
August 25, 2023
Study Start
December 18, 2023
Primary Completion
February 5, 2026
Study Completion (Estimated)
December 4, 2026
Last Updated
March 11, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share