Vemurafenib for Advanced Cancers with BRAF V600 Mutations

No longer recruiting at 124 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers, P-gp inhibitors

Disqualifiers: Pregnancy, Corticosteroids, Investigational drugs, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of vemurafenib in treating advanced cancers with BRAF V600 mutations, such as certain solid tumors and types of lymphoma, that have spread or resisted treatment. Vemurafenib may inhibit cancer cell growth by blocking specific enzymes they require. Individuals with these mutations who have not responded to other treatments might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop taking certain medications, such as other anti-cancer agents, investigational drugs, and specific drugs that affect liver enzymes (CYP3A4) and proteins (P-gp, ABCG2). If you're on these medications, you may need to stop them 14 days before joining the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that vemurafenib is likely to be safe for humans?

Research has shown that vemurafenib can be safely used in patients with advanced cancers that have a BRAF V600 mutation. In a study with patients who had metastatic melanoma (a type of skin cancer that has spread), vemurafenib helped shrink tumors and improved survival rates. Importantly, even after two years of follow-up, no new safety issues emerged, suggesting that the treatment remains safe over time.

For those considering joining a trial, these findings are promising. Vemurafenib has demonstrated good tolerance in past studies, with consistent safety results across different cancer types. However, discussing possible side effects and any personal health concerns with a healthcare provider is important before joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vemurafenib is unique because it specifically targets the BRAF V600 mutation found in some advanced cancers. Most treatments for these conditions, such as chemotherapy, work broadly and can affect both cancerous and healthy cells. In contrast, vemurafenib zeroes in on this specific genetic mutation, potentially leading to more effective treatment with fewer side effects. Researchers are excited about vemurafenib because it offers a more personalized approach, targeting the cancer at a molecular level and possibly improving outcomes for patients who have these specific genetic changes.

What evidence suggests that vemurafenib might be an effective treatment for advanced cancers with BRAF V600 mutations?

Research has shown that vemurafenib effectively treats cancers with BRAF V600 mutations. Studies have found that it helps patients live longer without disease progression and increases overall survival compared to chemotherapy. Vemurafenib has successfully controlled tumors in various advanced cancers. Specifically, patients with melanoma who took vemurafenib lived longer than those who did not. These findings suggest that vemurafenib could be a promising treatment for patients with advanced cancers that have the BRAF V600 mutation. Participants in this trial will receive vemurafenib as part of their treatment regimen. ^{2 6 7 8 9}

Who Is on the Research Team?

AeRang Kim

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for kids and teens with advanced solid tumors, lymphoma, or histiocytic disorders that have a specific mutation (BRAF V600) and haven't responded to other treatments. They should be recovering from previous therapies, able to perform daily activities at least minimally despite any neurological issues, and not have been treated with BRAF inhibitors before.

Inclusion Criteria

My cancer can be seen and measured on scans, or if I have neuroblastoma, it shows up on an MIBG scan.

I can do most daily activities by myself, even if I use a wheelchair.

All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

Patients who are currently receiving another investigational drug

I am taking medication to prevent graft-versus-host disease after a bone marrow transplant.

You have had an organ transplant in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vemurafenib orally twice daily in 28-day cycles, repeated for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term Follow-up

Participants are monitored for progression-free survival and changes in tumor genomics

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Vemurafenib

Trial Overview The study tests how well vemurafenib works on patients with certain mutations in their cancer cells. It's designed to see if this drug can stop the growth of tumor cells by blocking enzymes they need to grow. The trial includes lab biomarker analysis as part of its procedures.

How Is the Trial Designed?

Group I: Treatment (vemurafenib) Experimental Treatment 2 Interventions

Patients receive vemurafenib PO BID on day 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Zelboraf for:

• Unresectable or metastatic melanoma with BRAF V600E mutation
• Erdheim-Chester Disease (ECD) with BRAF V600 mutation

Approved in European Union as Zelboraf for:

• Adults with BRAF V600E mutation positive unresectable or metastatic melanoma

Approved in Canada as Zelboraf for:

• Unresectable or metastatic melanoma with BRAF V600E mutation

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3421463/

Vemurafenib: a new treatment for BRAF-V600 mutated ... The BRAF inhibitor, vemurafenib, has demonstrated improved progression-free and overall survival compared with chemotherapy in a randomized trial.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37922690/

Long term activity of vemurafenib in cancers with BRAF ... The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety. Results: ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1103782

Improved Survival with Vemurafenib in Melanoma ... Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2059702923012796

Long term activity of vemurafenib in cancers with BRAF ... Vemurafenib provides durable tumour control and survival in various advanced cancer types. Long-term survival is observed in rare and common histotypes.

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/10/5/657/2615/Pan-Cancer-Efficacy-of-Vemurafenib-in-BRAFV600

Pan-Cancer Efficacy of Vemurafenib in BRAF V600 -Mutant ... We now present the updated and final pan-cancer efficacy data for vemurafenib monotherapy in 172 patients with 26 unique BRAFV600-mutant cancer types. To ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24295639/

Vemurafenib in patients with BRAF(V600) mutation ... Vemurafenib can be safely used in patients with advanced symptomatic melanoma that has metastasised to the brain and can result in meaningful tumour regression.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4631301/

The outcomes of Polish patients with advanced BRAF-positive ... The BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1502309

Vemurafenib in Multiple Nonmelanoma Cancers with ... A total of 122 patients with BRAF V600 mutation–positive cancer were treated, including 27 patients with colorectal cancer who received ...

9. ejcancer.com ejcancer.com/article/S0959-8049(17)30884-5/abstract

Open-label, multicentre safety study of vemurafenib in 3219 ... We studied vemurafenib in BRAFV600 mutation-positive metastatic melanoma. •. After 2 years' follow-up, no new safety signals were seen and safety was maintained ...