Vemurafenib + Cobimetinib for Craniopharyngioma

Not currently recruiting at 123 trial locations

Overseen By Priscilla K. Brastianos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Congestive heart failure, Uncontrolled hypertension, 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: Unknown

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two medications, vemurafenib and cobimetinib, in treating craniopharyngioma, specifically when the BRAF V600E mutation is present. These drugs aim to halt tumor growth by blocking enzymes essential for cancer cell growth. Individuals with papillary craniopharyngioma who have this BRAF mutation and have undergone surgery or radiation may be suitable candidates for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. If you are on medications that are strong CYP3A4 inducers or inhibitors, or CYP1A2 substrates, you must stop them at least 14 days before joining the study.

Is there any evidence suggesting that vemurafenib and cobimetinib are likely to be safe for humans?

Research has shown that vemurafenib and cobimetinib are generally well-tolerated by patients with craniopharyngiomas. In one study, 94% of patients with BRAF-mutated craniopharyngioma showed at least partial improvement with these drugs, suggesting the treatment works well for many.

While the treatment appears promising, awareness of possible side effects is important. Some patients in studies experienced side effects, a common occurrence in cancer treatments. Discussing potential risks and benefits with a doctor is crucial.

The FDA has already approved vemurafenib and cobimetinib for other conditions, providing some reassurance about their safety. However, individual reactions may vary, so obtaining personal medical advice is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Vemurafenib and cobimetinib are unique because they specifically target genetic mutations found in some craniopharyngioma tumors, unlike traditional treatments like surgery and radiation. Vemurafenib works by inhibiting a specific protein (BRAF) that drives tumor growth, while cobimetinib blocks a different protein (MEK), helping to enhance the effects of vemurafenib. This combination approach could potentially offer a more tailored treatment option, reducing tumor size and delaying progression with fewer side effects compared to conventional therapies. Researchers are excited about these targeted treatments because they represent a shift towards more personalized medicine, which could improve outcomes for patients with this challenging condition.

What evidence suggests that vemurafenib and cobimetinib might be an effective treatment for craniopharyngioma?

Research has shown that using vemurafenib and cobimetinib together effectively treats craniopharyngiomas with the BRAF V600E mutation. In one study, almost all patients experienced significant tumor shrinkage, with a 94% response rate. This indicates that most patients receiving the treatment saw a noticeable reduction in tumor size. Other studies have also demonstrated that this combination can greatly slow disease progression. In this trial, participants will receive vemurafenib and cobimetinib, which could be effective options for managing this type of tumor. ^{1 3 4 6 7}

Who Is on the Research Team?

Priscilla K. Brastianos, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for patients with a specific brain tumor called BRAF V600E mutation positive craniopharyngioma. Eligible participants must have measurable disease, may or may not have received prior surgery, and should not have had previous treatment with BRAF or MEK inhibitors. Women of childbearing potential need a negative pregnancy test to participate.

Inclusion Criteria

I don't have a history of prolonged QT syndrome.

My kidney function is normal or only slightly reduced.

Absolute neutrophil count >= 1500/mm^3

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 on days 1-28 and cobimetinib once daily on days 1-21. Treatment repeats every 28 days for up to 5 courses.

20 weeks

Follow-up

Participants are monitored for disease progression or unacceptable toxicity. Patients with disease progression are followed up every 16 weeks for 2 years, and all other patients are followed up every 6 months for 5 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cobimetinib
• Vemurafenib

Trial Overview The effectiveness of two drugs, vemurafenib and cobimetinib, is being tested on stopping the growth of this type of brain tumor by blocking enzymes needed for cell growth. The study will assess how well these drugs work together in treating this condition.

How Is the Trial Designed?

Group I: Treatment (vemurafenib, cobimetinib) Experimental Treatment 4 Interventions

Patients receive vemurafenib PO BID on day 1-28 and cobimetinib PO QD on days 1-21. Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive radiation therapy, surgery, or continued treatment with vemurafenib and cobimetinib at the discretion of the treating physician.

Cobimetinib is already approved in European Union, United States, Canada, Switzerland, Japan for the following indications:

Approved in European Union as Cotellic for:

• Melanoma

Approved in United States as Cotellic for:

• Melanoma

Approved in Canada as Cotellic for:

• Melanoma

Approved in Switzerland as Cotellic for:

• Melanoma

Approved in Japan as Cotellic for:

• Melanoma

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

A patient with a BRAF-V600E mutant papillary craniopharyngioma showed significant tumor reduction and neurological improvement after treatment with a combination of BRAF and MEK inhibitors (dabrafenib and trametinib) following unsuccessful radiation therapy.

Despite the successful tumor response, the patient experienced permanent panhypopituitarism, highlighting the need to consider potential long-term side effects of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. Roque, A., Odia, Y.[2018]

Recent advances in understanding the molecular mechanisms of craniopharyngiomas have led to promising medical therapies, particularly for adamantinomatous craniopharyngiomas (ACPs) and papillary craniopharyngiomas (PCPs), which are characterized by distinct genetic mutations.

Targeted treatments, such as MEK inhibitors for ACPs and BRAF inhibitors for PCPs, have shown favorable responses in patients, indicating a shift towards personalized medicine for managing these rare tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Therapy for Craniopharyngiomas. Alexandraki, KI., Xekouki, P.[2022]

In a study of 666 adult patients with craniopharyngioma, factors such as older age, lack of insurance, and larger tumor size were linked to worse overall survival, highlighting the importance of these demographics in treatment outcomes.

Patients who underwent gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy experienced significantly improved overall survival, while endoscopic resection methods had lower GTR rates but did not affect overall survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Factors and Treatment Impact on Overall Survival in Adult Craniopharyngioma. Awad, M., Butterfield, JT., Dhawan, S., et al.[2023]

A 35-year-old man with a BRAF-V600E-positive papillary craniopharyngioma experienced a remarkable 95% reduction in tumor size over 21 months while being treated with the BRAF-V600 inhibitor dabrafenib and trametinib, indicating the efficacy of this targeted therapy.

The treatment was well-tolerated with no negative side effects reported, suggesting that BRAF-V600E inhibition could be a safe and effective non-invasive option for managing this type of tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report and literature review of BRAF-V600 inhibitors for treatment of papillary craniopharyngiomas: A potential treatment paradigm shift. Nussbaum, PE., Nussbaum, LA., Torok, CM., et al.[2022]

Vemurafenib combined with cobimetinib has shown effectiveness in treating patients with BRAF-mutant papillary craniopharyngioma, a type of brain tumor.

This combination therapy targets specific mutations, suggesting a tailored approach to treatment that could improve outcomes for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAF-MEK Inhibition Is Effective in BRAFV600E-Mutant Papillary Craniopharyngioma. [2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11131344/

Promising response to vemurafenib and cobimetinib ... This case report focuses on a patient with a complex strictly third ventricle papillary craniopharyngioma that underwent adjuvant BRAF/MAPK inhibitor therapy.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213329

BRAF–MEK Inhibition in Newly Diagnosed Papillary ... The results of this biomarker-driven trial for papillary craniopharyngiomas showed durable partial or better responses in all patients who ...

3. cancer.gov cancer.gov/news-events/cancer-currents-blog/2023/craniopharyngioma-zelboraf-cotellic

Changing Care for Craniopharyngioma - NCI For some people with craniopharyngioma, treatment with vemurafenib (Zelboraf) and cobimetinib (Cotellic) may substantially delay, ...

4. onclive.com onclive.com/view/vemurafenib-plus-cobimetinib-demonstrates-near-100-response-rate-in-papillary-craniopharyngiomas

Vemurafenib Plus Cobimetinib Demonstrates Near 100% ... The combination of vemurafenib and cobimetinib led to a 94% partial response rate or better in 16 patients with newly diagnosed BRAF-mutated ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20392183

Vemurafenib and Cobimetinib in Treating Patients With ... This phase II trial studies how well vemurafenib and cobimetinib work in treating patients with BRAF V600E mutation positive craniopharyngioma. Vemurafenib ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37437144/

BRAF-MEK Inhibition in Newly Diagnosed Papillary ... - PubMed In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03224767/

Clinical Trial: NCT03224767 Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Related Conditions:.