EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

NCT ID: NCT06011772

Last Updated: 2025-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-18

Study Completion Date

2026-12-04

Brief Summary

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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.

Detailed Description

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Primary Objective

\- Determine the immunogenicity of CIMAvax in patients with metastatic, KRAS/NRAS/BRAF wild type CRC in combination with Chemotherapy plus appropriate biologic agent in 1st or 2nd/3rd line setting and chemotherapy plus anti-EGFR therapy in 2nd/3rd line setting.

Conditions

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Colo-rectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A

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 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.

Group Type EXPERIMENTAL

Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Intervention Type BIOLOGICAL

Given IM

Leucovorin

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Irinotecan

Intervention Type DRUG

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Biospecimen collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Panitumumbab

Intervention Type BIOLOGICAL

Given IV

Cohort B

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 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.

Group Type EXPERIMENTAL

Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Intervention Type BIOLOGICAL

Given IM

Leucovorin

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Irinotecan

Intervention Type DRUG

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Biospecimen collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Panitumumbab

Intervention Type BIOLOGICAL

Given IV

Cohort C

Description 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.

Group Type EXPERIMENTAL

Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Intervention Type BIOLOGICAL

Given IM

Leucovorin

Intervention Type DRUG

Given IV

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Metastasectomy

Intervention Type PROCEDURE

Undergo metastasectomy

Biospecimen collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Interventions

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Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine

Given IM

Intervention Type BIOLOGICAL

Leucovorin

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Bevacizumab

Given IV

Intervention Type BIOLOGICAL

Irinotecan

Given IV

Intervention Type DRUG

Cetuximab

Given IV

Intervention Type BIOLOGICAL

Metastasectomy

Undergo metastasectomy

Intervention Type PROCEDURE

Biospecimen collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Panitumumbab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Cimavax CIMAvax EGF Epidermal Growth Factor (EGF) Vaccine CAT CAT SCAN ABX-EGF ABX-EGF Monoclonal Antibody

Eligibility Criteria

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Inclusion Criteria

* 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.
* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
* Participant agrees to provide paired-tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C)

Exclusion Criteria

* Toxicity ≥Grade 2 from prior chemotherapy with exception to Grade 2 peripheral neuropathy..
* Other cancer requiring active treatment.
* Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment is exclusionary to Cohort A and C only
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Deepak Vadehra

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Comprehensive Cancer Center

Locations

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Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Countries

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United States

Other Identifiers

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I 1578122

Identifier Type: -

Identifier Source: org_study_id

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