Anti-EGFR Therapy for Colorectal Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must be taking: EGFR inhibitors

Disqualifiers: BRAF V600 mutations, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: up to 5 years

71 Participants Needed

Trial Summary

What is the purpose of this trial?

The study will use previously established doses of panitumumab or cetuximab in the metastatic setting for the treatment of unresectable colorectal cancer (CRC). It is designed to investigate an alternative treatment strategy to maximize the benefit to inhibition of epidermal growth factor receptor (EGFR) for a highly selected patient population. It will enroll 71 participants with left-sided, unresectable metastatic CRC. Participants will be on study up to 5 years.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must not have any additional malignancy requiring systemic treatment, except for hormonal treatments for breast or prostate cancer, which are allowed.

What data supports the effectiveness of the drug for colorectal cancer?

Cetuximab, when used in combination with FOLFIRI (a chemotherapy regimen), has been shown to improve survival and response rates in patients with metastatic colorectal cancer that have specific genetic markers (KRAS wild-type). This suggests that cetuximab is effective in treating certain types of colorectal cancer. ^{1 2 3 4 5}

What safety data exists for anti-EGFR therapy in colorectal cancer?

Cetuximab and panitumumab, used for colorectal cancer, are generally well tolerated but can cause side effects like skin rash, infusion reactions, lung issues, and low magnesium levels. It's important to manage these side effects promptly to continue treatment safely. ^{1 3 5 6 7}

How is the drug Cetuximab unique in treating colorectal cancer?

Cetuximab is unique because it is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which helps slow the growth of cancer cells. It is particularly effective in patients with KRAS wild-type metastatic colorectal cancer and is often used in combination with other chemotherapy drugs to improve survival rates. ^{1 2 4 5 6}

Research Team

Dustin Deming, M.D.

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for adults with left-sided, unresectable metastatic colorectal cancer (mCRC) who haven't had major surgery in the last 2 weeks and have no other cancers needing treatment. They should not have large mCRC lesions (>3.5cm), must show stable organ function, and agree to use contraception if of childbearing potential. Participants can be new to treatment or may have previously responded to EGFR inhibitors.

Inclusion Criteria

No history of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or cetuximab, including known severe hypersensitivity reactions to monoclonal antibodies.

Evaluable disease according to RECIST v1.1. Participants do not have to have measureable disease

My recent tests show my organs are functioning well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive panitumumab or cetuximab in the metastatic setting for the treatment of unresectable colorectal cancer

up to 5 years

Day 1 and 15 of a 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 years

Extension

Participants may continue to be monitored for overall survival and progression-free survival

up to 4 years

Treatment Details

Interventions

• Cetuximab
• Panitumumab

Trial Overview The study tests established doses of panitumumab or cetuximab for treating mCRC, aiming to maximize benefits from blocking the epidermal growth factor receptor (EGFR). It's a strategy trial enrolling up to 110 patients who will receive treatments over a period that could extend up to five years.

Participant Groups

Group I: Cohort C: Rechallenge Experimental Treatment 4 Interventions

Participants with prior FOLFOX and either no prior EGFR inhibitor or treated on Cohort A. Alternating Panitumumab (6mg/kg) or Cetuximab 500mg (per treating physician) and 4 cycles of FOLFIRI +/- bevacizumab

Group II: Cohort B: Retreatment Experimental Treatment 3 Interventions

Participants with treatment refractory disease who have previously benefitted (greater than or equal to 4 months ago) from anti-EGFR therapy. Panitumumab (6mg/kg) or Cetuximab 500mg (per treating physician) on day 1 and 15 of a 28-day cycle, +/- Irinotecan (180mg/m\^2) every 2 two weeks per standard of care

Group III: Cohort A: No Previous EGFR Experimental Treatment 2 Interventions

Participant who have not be previously exposed to anti-EGFR therapies and are in the first or second-line metastatic treatment setting. Panitumumab (6mg/kg) or Cetuximab 500mg (per treating physician) on day 1 and 15 of a 28-day cycle

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

Findings from Research

Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) and show promise as therapies for colorectal cancer, particularly in cases where chemotherapy has failed.

The review discusses their effectiveness in both advanced and initial treatment settings, as well as factors that may predict patient response or resistance to these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of monoclonal antibodies to the epidermal growth factor receptor in colorectal cancer. Burtness, B.[2018]

Cetuximab and panitumumab are effective treatments for patients with previously untreated RAS wild-type metastatic colorectal cancer, showing cost-effectiveness when combined with standard chemotherapy regimens (FOLFOX or FOLFIRI) compared to chemotherapy alone.

Both drugs meet the National Institute for Health and Care Excellence's end-of-life criteria and are recommended for use within the UK National Health Service, indicating their potential benefit for patients not eligible for liver resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Analysis of First-Line Treatment with Cetuximab or Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer in England. Tikhonova, IA., Huxley, N., Snowsill, T., et al.[2021]

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 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]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Cetuximab and panitumumab, both targeting the EGFR, have been shown to improve progression-free and overall survival in patients with wild-type RAS metastatic colorectal cancer, highlighting their efficacy as treatment options.

Common side effects include dermatological issues like acneiform rash and hair changes, which are important to consider alongside the cost-effectiveness of these therapies in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of EGFR inhibitors in colorectal cancer: is it clinically efficacious and cost-effective? Lien, K., Berry, S., Ko, YJ., et al.[2018]

Cetuximab and panitumumab are effective treatments for colorectal cancer, showing clinical activity as anti-EGFR monoclonal antibodies, and are generally well tolerated by patients.

While these medications have fewer severe adverse events compared to traditional cytotoxic agents, they can still cause issues like infusion reactions, skin toxicity, lung toxicity, and low magnesium levels, which need to be managed promptly to avoid treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-epidermal growth factor receptor monoclonal antibodies induced adverse events]. Tsuji, Y., Kogawa, T., Abe, M.[2018]

References

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

Clinical use of monoclonal antibodies to the epidermal growth factor receptor in colorectal cancer. [2018]

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

Economic Analysis of First-Line Treatment with Cetuximab or Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer in England. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

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. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

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

The use of EGFR inhibitors in colorectal cancer: is it clinically efficacious and cost-effective? [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

[Anti-epidermal growth factor receptor monoclonal antibodies induced adverse events]. [2018]