Nivolumab + Standard Treatment for Colorectal Cancer

Not currently recruiting at 331 trial locations

Overseen By Deepak Vadehra

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: HIV antiretrovirals, BRAF inhibitors

Disqualifiers: HIV, Autoimmune diseases, Organ transplant, 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: Variable, based on disease progression

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding nivolumab to the standard treatment can more effectively shrink tumors in individuals with colorectal cancer that has spread or cannot be surgically removed. The trial compares the usual drugs, encorafenib and cetuximab, with and without nivolumab, which may enhance the body's immune response against cancer cells. Individuals with colorectal cancer that has a specific BRAF gene mutation, and whose cancer has spread or cannot be surgically removed, might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain HIV medications or if you have conditions requiring high doses of corticosteroids. It's best to discuss your current medications with the trial team to see if they might interfere with the study.

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

Research has shown that the combination of encorafenib, cetuximab, and nivolumab is generally safe and well-tolerated. One study found high success rates with this combination in patients with certain types of colorectal cancer. Specifically, it was safe for patients with microsatellite-stable BRAF-mutated colorectal cancer.

The FDA has already granted accelerated approval for using encorafenib and cetuximab with another chemotherapy for a type of advanced colorectal cancer. This indicates that the treatment has passed some safety checks for that condition. However, every treatment can have side effects.

Overall, evidence suggests these treatments are generally well-tolerated, but discussing potential risks and benefits with a healthcare provider is always best. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about the combination of nivolumab with encorafenib and cetuximab for colorectal cancer because it introduces a new way to boost the immune system against cancer cells. Unlike standard treatments like chemotherapy or targeted therapies alone, nivolumab is an immunotherapy that works by blocking a protein called PD-1, which can help the immune system better recognize and attack cancer cells. This combination aims to enhance the effectiveness of existing targeted therapies—encorafenib and cetuximab—by using the body's own defenses to fight the cancer more effectively. Overall, this approach could potentially improve outcomes for patients with colorectal cancer by offering a more comprehensive attack on tumor cells.

What evidence suggests that adding nivolumab to the standard treatment could be effective for metastatic or unresectable BRAF-mutant colorectal cancer?

This trial will compare two treatment arms for colorectal cancer patients with the BRAF mutation. In one arm, participants will receive encorafenib and cetuximab. Studies have indicated that this combination already helps some patients live longer. In the other arm, participants will receive encorafenib, cetuximab, and nivolumab. Research has shown that adding nivolumab may improve outcomes, with early results indicating that 50% of patients responded positively, such as experiencing tumor shrinkage. This combination also demonstrated an average survival time of 22 months, which is promising for patients with this type of cancer. Overall, these three drugs are thought to work well together because they target different ways the cancer grows and spreads. ^{1 4 6 7 8}

Who Is on the Research Team?

Van K Morris

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with metastatic or unresectable colorectal cancer that has a BRAF mutation. They should have had one or two prior chemotherapy treatments, no severe heart conditions, and be able to swallow pills. Excluded are those with recent heart issues, uncontrolled hypertension, active infections like HIV, certain immune diseases, or who've had specific past treatments like anti-EGFR therapies.

Inclusion Criteria

I have chronic hepatitis B but it's under control with medication.

My scans show cancer that cannot be removed or has spread.

Participants must be informed of the investigational nature of the study and provide informed consent

Exclusion Criteria

Participants must not be pregnant or nursing and must agree to use effective contraception

I have not had any major heart problems recently.

Participants must not be receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive encorafenib and cetuximab, with or without nivolumab, in 28-day cycles until disease progression or unacceptable toxicity

Variable, based on disease progression

Visits on days 1 and 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Encorafenib
• Nivolumab

Trial Overview The study tests if adding Nivolumab (an immunotherapy drug) to the standard treatment of Encorafenib and Cetuximab improves outcomes in patients. It's a phase II trial aiming to see if this combination better shrinks tumors compared to the usual treatment alone.

How Is the Trial Designed?

Group I: Arm I (encorafenib, cetuximab, nivolumab) Experimental Treatment 3 Interventions

Patients receive encorafenib PO QD on days 1-28, cetuximab IV on days 1 and 15, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (encorafenib, cetuximab) Active Control 2 Interventions

Patients receive encorafenib PO QD on days 1-28 and cetuximab IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cetuximab, an EGFR-inhibiting antibody used for treating certain cancers, is generally considered safe and well-tolerated, but this case highlights the potential for severe complications following its use, particularly in complex surgical situations.

The patient experienced a rare and fatal combination of complications after surgery, raising concerns about the safety of cetuximab in the context of surgical procedures, and emphasizing the need for careful monitoring and documentation of adverse effects in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. Knauer, M., Haid, A., Ammann, K., et al.[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, when combined with irinotecan, can provide patients with metastatic colorectal cancer an additional 1.7 to 2.0 years of life, indicating its efficacy as a treatment option.

However, the cost-effectiveness analysis revealed that the treatment is quite expensive, with costs per life year gained ranging from 205,536 to 323,040 Euros, highlighting the financial considerations of using cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. Norum, J.[2019]

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]

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, 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 the BEACON CRC clinical trial, the combination of encorafenib and cetuximab significantly improved median overall survival and progression-free survival in adults with metastatic colorectal cancer harboring a BRAF V600E mutation, compared to standard therapies.

The treatment was found to have a manageable safety profile, making it a promising targeted option for patients who have already undergone previous systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib: A Review in Metastatic Colorectal Cancer with a BRAF V600E Mutation. Al-Salama, ZT.[2021]

Citations

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Pfizer's BRAFTOVI® Combination Regimen Cuts the Risk ... Pivotal results from the Phase 3 BREAKWATER trial showed 51% risk reduction in death compared to standard-of-care treatment BRAFTOVI ...

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Combination of Encorafenib and Cetuximab With ... Combination of Encorafenib and Cetuximab With Chemotherapy Helps Some Patients With Advanced Colorectal Cancer Live Longer. Combination of ...

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Braftovi and Erbitux Plus Chemo Improves Outcomes for ... Data from the cohort of patients who received Braftovi plus Erbitux without chemo showed that the median progression-free survival was 6.8 ...

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FDA grants accelerated approval to encorafenib with ... FDA grants accelerated approval to encorafenib with cetuximab and mFOLFOX6 for metastatic colorectal cancer with a BRAF V600E mutation.

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Management of adverse events from the treatment ... Data from the phase III BEACON CRC study indicate that the combination of encorafenib with cetuximab has a distinct safety profile. Here we ...

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NCT04607421 | A Study of Encorafenib Plus Cetuximab ... The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes ...