BRAF-Targeted Therapy for Colon Cancer

Recruiting at 225 trial locations

Overseen By Jamie Crawley

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: QTc-prolonging drugs, CYP3A4 inhibitors

Disqualifiers: Uncontrolled infection, Diabetes, Cardiac disease, 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: 6 months

Trial Summary

What is the purpose of this trial?

This phase II/III trial compares treatment with encorafenib and cetuximab to usual care (patient observation) for reducing the chance of cancer recurrence after standard surgery and chemotherapy in patients with BRAF-mutated stage IIB-III colon cancer. Encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Giving encorafenib and cetuximab after standard surgery and chemotherapy may be more effective at reducing the chance of cancer recurrence compared to the usual patient observation.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you must stop taking strong CYP3A4 inhibitors and inducers 14 days before starting the trial. Also, avoid drugs that prolong the QTc interval if possible.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers at least 14 days before joining the study. Also, if you're on medications that prolong the QTc interval, you should avoid them if possible, as they can interact with the trial drugs.

What data supports the idea that BRAF-Targeted Therapy for Colon Cancer is an effective treatment?

The available research shows that BRAF-Targeted Therapy, specifically using the drug cetuximab, is effective for treating colon cancer. In one study, cetuximab combined with another treatment called FOLFIRI improved the time patients lived without the cancer getting worse and increased overall survival compared to FOLFIRI alone. Another study reported that 6 out of 8 patients with advanced colon cancer responded well to cetuximab, with significant tumor shrinkage and reduced cancer markers. Additionally, a combination of encorafenib and cetuximab showed better survival rates compared to other treatments in patients with a specific mutation. These findings suggest that BRAF-Targeted Therapy can be a beneficial option for colon cancer patients. ^{1 2 3 4 5}

What data supports the effectiveness of the drug BRAF-Targeted Therapy for Colon Cancer?

Research shows that cetuximab, when used with other treatments, improves survival and response rates in patients with certain types of metastatic colorectal cancer. Additionally, encorafenib combined with cetuximab has been shown to extend survival in patients with a specific mutation (BRAFV600E) in their colorectal cancer. ^{1 2 3 4 5}

What safety data is available for BRAF-targeted therapy in colon cancer?

Cetuximab (Erbitux) has been evaluated for safety in several studies. A Japanese post-marketing surveillance study confirmed its safety in practical use for metastatic colorectal cancer. Common side effects include dermatological issues such as acneiform rash and paronychia. These side effects were observed in all patients in a study involving cetuximab monotherapy and combination therapy. Additionally, cetuximab has been used in combination with FOLFIRI, improving progression-free survival and overall survival in patients with KRAS wild-type tumors. The most common side effects are dermatological, including skin rash, pruritus, and hair changes. ^{1 2 3 5 6}

What safety data exists for BRAF-targeted therapy using Cetuximab in colon cancer?

Cetuximab, used for treating metastatic colorectal cancer, has been associated with common side effects like skin rash and nail infections. These side effects were observed in all patients in a study, indicating they are relatively common when using this treatment. ^{1 2 3 5 6}

Is the drug used in the trial 'BRAF-Targeted Therapy for Colon Cancer' a promising treatment?

The drug cetuximab is a promising treatment for colon cancer. It targets specific cancer cells, helping to slow down or stop the growth of tumors. Studies show that cetuximab, especially when combined with other treatments, can improve survival rates and reduce tumor size in patients with certain types of colon cancer. ^{1 2 3 5 7}

How does BRAF-targeted therapy for colon cancer differ from other treatments?

BRAF-targeted therapy for colon cancer is unique because it specifically targets the BRAF gene mutation, which is a different approach compared to treatments like cetuximab that target the epidermal growth factor receptor (EGFR). This makes BRAF-targeted therapy potentially more effective for patients with BRAF-mutated colon cancer, as it directly addresses the genetic mutation driving the cancer's growth. ^{1 2 3 5 7}

Eligibility Criteria

This trial is for adults with stage IIB-III colon cancer that has been surgically removed and treated with specific chemotherapy. Participants must have a BRAF V600E mutation, stable microsatellite status, proper organ function, no severe heart conditions or uncontrolled hypertension, not be pregnant or nursing, and cannot have other active cancers or serious medical issues.

Inclusion Criteria

My tumor is microsatellite stable.

Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

Total bilirubin =< 1.5 x upper limit of normal (ULN)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive encorafenib orally and cetuximab intravenously, with blood samples collected throughout the study

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CT or MRI scans

up to 6 years

Periodic visits for imaging and assessments

Observation

Patients undergo observation per usual care, with blood samples collected and imaging during follow-up

up to 6 years

Treatment Details

Interventions

• Cetuximab
• Encorafenib

Trial Overview The study compares the effectiveness of encorafenib plus cetuximab (targeting enzymes and proteins to stop tumor growth) against usual care after surgery and chemotherapy in preventing cancer recurrence in patients with certain genetic mutations in their colon cancer.

Participant Groups

Group I: Arm I (encorafenib, cetuximab) Experimental Treatment 5 Interventions

Patients receive encorafenib PO and cetuximab IV on study. Patients also undergo collection of blood samples throughout the study and CT or MRI during screening and follow-up.

Group II: Arm II (patient observation) Active Control 4 Interventions

Patients undergo observation per usual care on study. Patients also undergo collection of blood samples throughout the study and CT or MRI during screening and follow-up.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

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]

Encorafenib in combination with cetuximab significantly improves overall survival (9.3 months) and progression-free survival (4.27 months) in adult patients with metastatic colorectal carcinoma (mCRC) with the BRAFV600E mutation compared to standard treatments, showing a hazard ratio of 0.61 for overall survival and 0.44 for progression-free survival.

The most common side effects reported with this treatment combination include fatigue, nausea, and skin-related issues, indicating that while the treatment is effective, it does come with a range of manageable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA assessment of encorafenib in combination with cetuximab for the treatment of adult patients with metastatic colorectal carcinoma harbouring the BRAFV600E mutation who have received prior therapy. Trullas, A., Delgado, J., Koenig, J., 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 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 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]

References

1. 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]

2. Japan pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]

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

Cetuximab. [2020]

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

The EMA assessment of encorafenib in combination with cetuximab for the treatment of adult patients with metastatic colorectal carcinoma harbouring the BRAFV600E mutation who have received prior therapy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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