EGF-Depleting Vaccine + Standard Therapy for Colorectal Cancer

Overseen By Deepak Vadehra

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: Anti-EGFR antibodies

Disqualifiers: Other cancer, Brain metastases, Immunosuppressive disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 7 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

42 Participants Needed

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that participants should not have toxicity from prior chemotherapy or other serious uncontrolled medical conditions. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

What data supports the idea that EGF-Depleting Vaccine + Standard Therapy for Colorectal Cancer is an effective treatment?

The available research shows that the EGF-Depleting Vaccine, known as CIMAvax-EGF, has been studied extensively for non-small cell lung cancer (NSCLC), not colorectal cancer. In these studies, the vaccine has shown to improve survival rates and is safe to use, even over long periods. Patients with higher levels of a specific protein in their blood had better outcomes when treated with this vaccine compared to those who received only supportive care. However, there is no specific data provided here about its effectiveness for colorectal cancer. ^{1 2 3 4 5}

What safety data exists for the EGF-depleting vaccine treatment?

The EGF-depleting vaccine, known as CIMAvax-EGF, has been studied for safety in both animal and human trials. In animal studies, repeated intramuscular doses in rats showed local damage at the injection site, such as cysts and granulomas, and systemic effects like increased neutrophils and AST levels, likely due to inflammation from the adjuvant Montanide ISA 51. However, the vaccine was generally well tolerated over 26 weeks. In human trials, particularly in patients with non-small cell lung cancer (NSCLC), the most common adverse events were pain, induration, and erythema at the injection site. Overall, the vaccine was considered safe and effective as a maintenance therapy in NSCLC patients. ^{1 2 3 6 7}

Is the treatment CIMAvax-EGF a promising treatment for colorectal cancer?

CIMAvax-EGF is a promising treatment because it helps the body's immune system fight cancer by targeting a specific growth factor that cancer cells need to grow. It has shown benefits in lung cancer, suggesting it could be effective for other cancers like colorectal cancer. ^{1 2 3 6 7}

What is the purpose of this trial?

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.

Research Team

Deepak Vadehra

Principal Investigator

Roswell Park Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with metastatic colorectal cancer that hasn't spread to the brain, who haven't had certain treatments or surgeries recently. They should have a type of cancer not affected by RAS/BRAF mutations and be in good physical condition. Participants must not have other active cancers, serious heart conditions, uncontrolled high blood pressure, significant infections, or immune diseases like HIV.

Inclusion Criteria

I am fully active or can carry out light work.

My colorectal cancer is RAS- and BRAF wild-type, untreated for advanced disease, and I am a candidate for surgery to remove liver metastases.

I have had 1 or 2 treatments for my advanced disease.

Exclusion Criteria

I have experienced significant side effects from previous chemotherapy.

I have been treated with anti-EGFR drugs for colorectal cancer.

I have brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

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.

8 weeks

2 visits (in-person) per cycle

Maintenance Phase

Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles. Patients also receive chemotherapy and undergo collection of blood samples throughout the trial.

40 weeks

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• CIMAvax-EGF

Trial Overview The study tests CIMAvax-EGF vaccine's ability to trigger an anti-cancer immune response when combined with standard therapies (like chemotherapy and biological agents) in patients with specific types of advanced colorectal cancer. It aims to see if this combination can improve treatment outcomes.

Participant Groups

Group I: Cohort C Experimental Treatment 6 Interventions

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 II: Cohort B Experimental Treatment 10 Interventions

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 III: Cohort A Experimental Treatment 10 Interventions

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.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Findings from Research

CIMAvax EGF, a therapeutic vaccine for advanced non-small-cell lung cancer (NSCLC), has shown significant efficacy in inducing an immune response against epidermal growth factor (EGF), leading to longer survival rates in vaccinated patients compared to controls, particularly in those under 60 years old.

The vaccine demonstrated a mild-to-moderate adverse event profile, indicating it is generally safe for chronic use, but further evaluation is needed for its benefits in earlier stages of NSCLC and in patients who cannot undergo chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy. Rodríguez, PC., Rodríguez, G., González, G., et al.[2021]

CIMAvax-EGF, a therapeutic cancer vaccine for non-small cell lung cancer (NSCLC), was found to be safe with mild adverse reactions, and it successfully induced anti-EGF antibodies while decreasing serum EGF levels.

Patients with advanced NSCLC who received the vaccine showed a median survival time of 12.43 months when they completed at least four doses, compared to 9.43 months in the control group, indicating a significant survival benefit linked to the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients. Rodriguez, PC., Popa, X., Martínez, O., et al.[2018]

CIMAvax-EGF, when combined with nivolumab, was found to be safe and tolerable for patients with advanced non-small cell lung cancer, with a recommended phase 2 dose established at 2.4 mg.

The combination therapy resulted in a quicker and more robust immune response, with 33% of evaluable patients showing an objective response, indicating potential efficacy in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC. Evans, R., Lee, K., Wallace, PK., et al.[2022]

CimaVax-EGF, a therapeutic cancer vaccine targeting Epidermal Growth Factor (EGF), has been safely administered to over 1000 advanced non-small cell lung cancer (NSCLC) patients, showing manageable side effects like mild injection site reactions and fever.

High-dose vaccination at multiple sites led to a significant increase in antibody response and a faster decrease in circulating EGF, suggesting potential improvements in survival rates for patients classified as good responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients. Rodriguez, PC., Neninger, E., García, B., et al.[2021]

CIMAvax-EGF is a safe treatment for advanced non-small cell lung cancer (NSCLC) that effectively reduces EGF serum levels and has been shown to increase median overall survival in patients with stable disease after chemotherapy, particularly in those with high serum EGF concentrations.

The study suggests that combining CIMAvax-EGF with existing therapies like tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) could enhance treatment outcomes and help manage advanced cancer as a chronic condition, improving patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer. Crombet Ramos, T., Santos Morales, O., Dy, GK., et al.[2022]

CIMAvax-EGF, a vaccine designed to inhibit the interaction between epidermal growth factor (EGF) and its receptor, was found to be well tolerated in Sprague Dawley rats over a 26-week study, even at doses up to 15 times the human total dose.

While the vaccine induced a specific immune response and did not affect overall body weight or food consumption, it did cause local inflammation and tissue damage at the injection site, likely due to the oil-based adjuvant Montanide ISA 51.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity. Mancebo, A., Casacó, A., González, B., et al.[2013]

CIMAvax-EGF, a therapeutic vaccine targeting EGFR in non-small cell lung cancer (NSCLC), demonstrated safety and efficacy in a study of 106 patients, with a median survival time of 14.6 months and a median progression-free survival of 8.16 months.

The treatment was well-tolerated, with common side effects including injection site pain (27.3%) and local erythema (10.9%), indicating that CIMAvax-EGF can be a viable maintenance therapy for NSCLC patients after first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival of NSCLC Patients Treated with Cimavax-EGF as Switch Maintenance in the Real-World Scenario. Flores Vega, YI., Páramo González, DL., Alsina Sarmiento, SC., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity. [2013]

7. Australia pubmed.ncbi.nlm.nih.gov

Survival of NSCLC Patients Treated with Cimavax-EGF as Switch Maintenance in the Real-World Scenario. [2023]