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

Colo-rectal Cancer Clinical Trial

Official title:

A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06011772
• Other study ID #: I 1578122
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 4, 2023
• Est. completion date: December 4, 2026

Study information

• Verified date: May 2024
• Source: Roswell Park Cancer Institute
• Contact: Deepak Vadehra
• Phone: 716-845-2300
• Email: askroswell[@]roswellpark.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 4, 2026
• Est. primary completion date: December 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 mFOLFOX6± Bevacizumab or mFOLFOX6± anti-EGFR therapy 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 liver metastasectomy (one cycle of standard therapy with mFOLFOX6 with or without appropriate biologic agent is allowed)

• KRAS/NRAS/BRAF wild-type.

• Have an ECOG Performance Status of 0 1. Refer to Appendix A.

• Patients must have adequate organ and marrow function as defined below:

• Absolute neutrophil count (ANC) = 1.5 x 109/L

• Platelets = 100 x 109/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 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.

• Other cancer requiring active treatment.

• Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment.

• 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 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.

Related Conditions & MeSH terms

• Colo-rectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given IM

Drug:
• Leucovorin
Given IV
• Oxaliplatin
Given IV
• Fluorouracil
Given IV

Biological:
• Bevacizumab
Given IV

Drug:
• Irinotecan
Given IV

Biological:
• Cetuximab
Given IV

Procedure:
• Metastasectomy
Undergo metastasectomy
• Biospecimen collection
Undergo collection of blood samples
• Computed Tomography
Undergo CT

Biological:
• Panitumumbab
Given IV

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression free survival		time from treatment until disease progression, death or last follow up assesed up to 2 years