BRAF-Targeted Therapy for Colon Cancer

Not currently recruiting at 230 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, encorafenib and cetuximab, can more effectively reduce the risk of colon cancer returning compared to post-surgery and chemotherapy monitoring. Encorafenib may inhibit tumor growth by blocking enzymes essential for cell growth, while cetuximab binds to a protein on tumor cells to prevent their growth. The trial seeks participants with BRAF-mutated stage IIB-III colon cancer who have completed surgery and chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that the combination of encorafenib and cetuximab is generally safe for people. Studies have found that individuals with BRAF-mutated cancers tolerate this treatment well. Importantly, real-world evidence indicates that it does not cause severe side effects in most patients. However, like any treatment, some people might experience mild to moderate side effects, such as tiredness or skin issues, but these are usually manageable.

Additionally, the combination of encorafenib and cetuximab is approved for use in certain types of colorectal cancer, indicating it has been evaluated for safety in humans. Overall, current data supports this combination as a safe option for treating BRAF-mutated colon cancer. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for colon cancer?

Researchers are excited about the combination of encorafenib and cetuximab for treating colon cancer because this duo targets the BRAF mutation, which is present in some aggressive cancer types. Most traditional treatments focus on chemotherapy, but encorafenib directly inhibits the BRAF protein, disrupting cancer cell growth. Meanwhile, cetuximab works by blocking the epidermal growth factor receptor (EGFR), which is often overactive in cancer cells, enhancing the treatment's effectiveness. This targeted approach offers a more personalized therapy, potentially improving outcomes for patients with BRAF-mutated colon cancer.

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

Research has shown that using encorafenib and cetuximab together effectively treats a specific type of colorectal cancer with a BRAF V600E mutation. One study found that this combination improved survival rates for patients whose cancer had spread to other parts of the body. This improvement occurred when these drugs were used with chemotherapy like mFOLFOX6. In this trial, participants in Arm I will receive encorafenib and cetuximab. Encorafenib blocks enzymes that help tumors grow, while cetuximab targets a protein called EGFR on cancer cells. This dual action helps stop cancer cells from multiplying. These treatments together have shown promising results in patients with similar genetic mutations. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2501912

Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated ... Data have been limited with respect to first-line treatment targeting the activation pathway that can show improved efficacy in BRAF V600E– ...

2. nature.com nature.com/articles/s41591-024-03443-3

Encorafenib, cetuximab and chemotherapy in BRAF- ... Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study.

3. asco.org asco.org/about-asco/press-center/news-releases/combination-encorafenib-cetuximab-chemotherapy-helps-patients-advanced-colorectal-cancer-live-longer

Combination of Encorafenib and Cetuximab With ... The targeted therapy combination of encorafenib and cetuximab with mFOLFOX6 chemotherapy helps patients with BRAF V600E-mutant metastatic colorectal cancer ( ...

4. mdanderson.org mdanderson.org/newsroom/asco-triple-therapy-regimen-significantly-improves-survival-in-BRAF-V600E-mutated-metastatic-colorectal-cancer.h00-159776445.html

ASCO: Triple therapy regimen significantly improves ... First-line treatment with the triplet combination of encorafenib, cetuximab and mFOLFOX6 significantly improved survival compared to the standard of care.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S104084282500335X

Targeted doublet therapy with encorafenib and cetuximab ... This study summarizes the results of nine clinical studies evaluating the combination of encorafenib and cetuximab in patients with BRAF V600E-mutated ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S294982012400033X

Safety and efficacy of encorafenib–cetuximab combination ... Safety and efficacy of encorafenib–cetuximab combination in BRAFV600E-mutated metastatic colorectal cancer: real-world evidence from the CONFIDENCE Spanish ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9271477/

Quality of life with encorafenib plus cetuximab with or ... In addition to improving OS, encorafenib plus cetuximab with or without binimetinib delays QoL decline in previously treated patients with BRAF V600E-mutant ...

8. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-braftovir-combination-regimen-cuts-risk-death-half

Pfizer's BRAFTOVI® Combination Regimen Cuts the Risk ... The BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab.