Immunotherapy + Cetuximab for Colon Cancer

Overseen By Maria Morelli

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antibiotics, Immunosuppressants, Vaccines, others

Disqualifiers: Autoimmune disease, Transplantation, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

A study of immunotherapy with expanded CB-NK cells in combination with cetuximab, to evaluate activity against minimal residual disease in patients with colon cancer that have completed adjuvant treatment but are positive for ctDNA

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic immunosuppressive medications, you may need to stop them at least 2 weeks before starting the study treatment. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination including Cetuximab for colon cancer?

Research shows that Cetuximab, when used with other chemotherapy drugs, improves survival and response rates in patients with metastatic colorectal cancer. It works by targeting the epidermal growth factor receptor (EGFR), which is involved in cancer cell growth, and has shown effectiveness particularly in patients with specific genetic markers. ^{1 2 3 4 5}

Is the combination of immunotherapy and cetuximab safe for humans?

Cetuximab, used in treating colorectal cancer, is generally considered safe with manageable side effects. Common side effects include skin reactions like acne, nail disorders, and infusion reactions, which can be serious but are typically manageable with proper medical supervision. ^{6 7 8 9 10}

What makes the drug combination of Immunotherapy + Cetuximab unique for colon cancer treatment?

This treatment is unique because it combines immunotherapy with cetuximab, a drug that targets the epidermal growth factor receptor (EGFR), enhancing the body's immune response to fight cancer cells. The addition of cetuximab to immunotherapy may improve the effectiveness of treatment by leveraging both the immune system and targeted therapy to attack cancer cells more effectively. ^{1 3 4 10 11}

Research Team

Maria Morelli

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with high-risk stage II or III colorectal cancer who've finished standard treatment and show no relapse but have ctDNA in their blood, or those with resected stage IV treated with curative intent. Participants must be healthy enough for the trial, not pregnant, without severe allergies to certain antibodies or components of the therapy, free from other cancers within 5 years, and not recently treated with similar drugs.

Inclusion Criteria

Has signed the Informed Consent Form

I had surgery for stage IV colorectal cancer, finished all treatments, have no visible cancer left, but still have cancer DNA in my blood.

I am fully active or can carry out light work.

Exclusion Criteria

Is pregnant or breastfeeding, or intends to become pregnant during the study

I have not taken any antibiotics by mouth or IV in the last 2 weeks.

Received treatment with an investigational therapy within 28 days prior to initiation of study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CB-NK cell infusion in combination with cetuximab

6 weeks

Follow-up

Participants are monitored for ctDNA clearance and safety after treatment

4 weeks

Treatment Details

Interventions

• CB-NK-TGF-βR2-/NR3C1
• Cetuximab
• Cyclophosphamide
• Fludarabine phosphate

Trial Overview The study tests a combination of immunotherapy using CB-NK cells pre-activated and expanded ex vivo along with cetuximab against minimal residual disease in colon cancer patients. It aims to see if this can target remaining cancer indicated by circulating tumor DNA (ctDNA) after primary treatment.

Participant Groups

Group I: Cetuximab Experimental Treatment 4 Interventions

given to patients with high-risk colorectal cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

The CIFRA study is investigating the effectiveness of cetuximab combined with irinotecan and fluorouracil in patients with metastatic colorectal cancer who have a specific genetic profile (FcγRIIIa V/V), which may enhance the drug's action through a mechanism called Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).

This phase II trial aims to determine if patients with the FcγRIIIa V/V genotype have a higher response rate to cetuximab, potentially improving treatment outcomes, while also assessing safety and survival metrics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. Ottaiano, A., Scala, S., Normanno, N., et al.[2020]

In a study of 57 patients with KRAS wild-type metastatic colorectal cancer, those with the EGFR CA repeat genotype of 36 or more showed a trend towards longer overall survival when treated with cetuximab and FOLFIRI, suggesting a potential genetic influence on treatment outcomes.

The presence of specific FcγR haplotypes (131H and 158V alleles) was linked to a lower response rate to cetuximab, indicating that genetic variations may affect the efficacy of this treatment in mCRC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer. Inoue, Y., Hazama, S., Iwamoto, S., et al.[2021]

Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth-factor receptor (EGFR) and has been clinically approved in Europe for treating metastatic colorectal cancer and locally advanced head and neck cancer since 2004 and 2006, respectively.

The review discusses cetuximab's established role in colorectal cancer treatment, ongoing studies, and future challenges, highlighting its significance as the leading anti-EGFR monoclonal antibody in clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: appraisal of a novel drug against colorectal cancer. Hildebrandt, B., le Coutre, P., Nicolaou, A., et al.[2019]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

The combination of anti-EGFR antibody Erbitux (cetuximab) and anti-VEGFR2 antibody DC101 demonstrated significant antitumor synergy in preclinical models of pancreatic and colon cancer, with a combination index indicating strong interaction (CI = 0.1, P < 0.01).

This synergistic effect is likely due to overlapping impacts on tumor cell proliferation and vascularization, with VEGF production and hypoxia-inducible factor 1alpha serving as potential molecular links between the two pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Tonra, JR., Deevi, DS., Corcoran, E., et al.[2018]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

Cetuximab, a monoclonal antibody targeting EGFR, showed a tumor growth control rate of 38% and a mean overall survival of 49.4 weeks in 24 patients with chemotherapy-refractory metastatic colorectal cancer, indicating its efficacy as a salvage therapy.

The treatment was associated with manageable side effects, the most common being skin reactions (67% reported acne), and other adverse effects included hypocalcemia (50%) and stomatitis (20%), suggesting that while cetuximab is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report. Mekata, E., Endo, Y., Sonoda, H., et al.[2021]

Cetuximab is an effective monoclonal antibody that targets the epidermal growth factor receptor, which is linked to poor outcomes in solid tumors, by blocking its activation and associated oncogenic processes.

While cetuximab can cause infusion reactions and skin-related side effects, its overall safety profile is favorable compared to traditional chemotherapy, and these side effects are generally manageable with appropriate treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: adverse event profile and recommendations for toxicity management. Thomas, M.[2020]

In a review of clinical trials for colorectal cancer, 76.9% of studies on cetuximab reported dermatologic adverse drug reactions (dADRs), with 50% showing a positive correlation between these reactions and patient survival, indicating that dADRs may be relevant for treatment outcomes.

In contrast, only 42.9% of studies on panitumumab reported dADRs, highlighting significant variability in reporting practices, which limits the ability to assess patient risk and compare the safety profiles of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. Bauer, KA., Hammerman, S., Rapoport, B., et al.[2018]

Cetuximab is an effective monoclonal antibody that targets the epidermal growth factor receptor, showing significant clinical efficacy in treating colorectal cancer (CRC) either alone or in combination with chemotherapy.

The combination of cetuximab with chemotherapy is well tolerated, with minimal overlapping toxicities, making it a crucial treatment option for patients with metastatic CRC who do not respond to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract. Mahtani, RL., Macdonald, JS.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Cetuximab: appraisal of a novel drug against colorectal cancer. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]

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

Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. [2018]

6. England pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report. [2021]

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

Cetuximab: adverse event profile and recommendations for toxicity management. [2020]

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

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. [2018]

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

An Update of Efficacy and Safety of Cetuximab in Metastatic Colorectal Cancer: A Narrative Review. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract. [2022]