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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to use two drugs, cetuximab and panitumumab, for treating advanced colorectal cancer that cannot be surgically removed. The goal is to enhance the effectiveness of blocking a specific protein (EGFR) that promotes cancer growth. Participants are divided into three groups: those who have not tried these drugs, those who benefited from them in the past, and those who have not used certain related treatments. Individuals with left-sided, advanced colorectal cancer that has spread, but without large tumors over 3.5 cm, might be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both cetuximab and panitumumab have been studied for their safety in treating metastatic colorectal cancer (mCRC). Cetuximab treats patients with a specific type of mCRC called K-Ras wild-type. Safety data indicates it is generally well-tolerated, though some patients experience side effects like skin reactions and low magnesium levels, common with this treatment type.

Panitumumab is also approved for patients with a similar type of mCRC and shares a safety profile with cetuximab. In studies, patients reported side effects such as skin rash and low calcium levels.

Both treatments are FDA-approved for certain types of colorectal cancer, having undergone rigorous testing to ensure general safety for humans. While side effects can occur, they are often manageable with the help of a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cetuximab and Panitumumab for colorectal cancer because these treatments specifically target the epidermal growth factor receptor (EGFR), which is often overexpressed in colorectal cancer cells. Unlike traditional chemotherapy that attacks rapidly dividing cells indiscriminately, these drugs work by blocking signals that promote cancer cell growth, offering a more targeted approach. Additionally, the trial includes varying strategies like rechallenge and retreatment, aiming to explore the potential benefits of reintroducing these therapies in patients who have previously been treated, which is a novel approach in managing treatment-resistant cases.

What evidence suggests that this trial's treatments could be effective for unresectable colorectal cancer?

In this trial, participants will receive either cetuximab or panitumumab as part of different treatment arms. Studies have shown that cetuximab can extend the lives of patients with advanced colorectal cancer, especially when combined with chemotherapy. Research also indicates that panitumumab, another treatment option in this trial, can improve survival for patients with tumors on the left side of the colon. Specifically, some studies found that patients who received panitumumab lived several months longer than those who only had chemotherapy. Both treatments target a protein called EGFR, which plays a role in cancer cell growth, offering hope for those with colorectal cancer that cannot be surgically removed. ^{6 7 8 9 10}

Who Is on the Research Team?

Dustin Deming, M.D.

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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Cetuximab - StatPearls - NCBI Bookshelf - NIH

Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor with the following FDA-approved indications: colorectal cancer, metastatic, KRAS wild-type ( ...