17 Participants Needed

Cobimetinib for Arteriovenous Malformations

JM
DP
DP
Overseen ByD'Ann Pierce, BSN
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 5 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial requires you to stop taking strong inducers or inhibitors of CYP3A4, such as certain antibiotics and herbal supplements, at least 14 days before starting the study. If you are on any chemotherapy, immunotherapy, or targeted therapy, you must have completed it and recovered from any side effects at least 28 days before joining the trial.

What data supports the effectiveness of the drug Cobimetinib for treating arteriovenous malformations?

Cobimetinib, when combined with vemurafenib, has been shown to improve survival and tumor response rates in patients with a specific type of skin cancer (melanoma) that has a BRAF V600 mutation. While this data is specific to melanoma, it suggests that Cobimetinib can be effective in targeting certain pathways involved in tumor growth.12345

Is cobimetinib safe for humans?

Cobimetinib has been generally well tolerated in humans, with common side effects including diarrhea, rash, fatigue, and nausea. Serious side effects have been observed, such as severe diarrhea and rash, but these are less common. No new safety concerns have been identified in recent studies.12678

How does the drug Cobimetinib differ from other treatments for arteriovenous malformations?

Cobimetinib is unique because it targets the MEK pathway, which is part of the RAS/RAF/MEK/ERK signaling cascade often involved in arteriovenous malformations with KRAS mutations. This approach is novel as it uses a mechanism similar to that of cancer treatments, focusing on specific genetic mutations rather than traditional surgical or embolization methods.910111213

What is the purpose of this trial?

The purpose of this open-label study is to evaluate the safety and efficacy of cobimetinib in extracranial AVM.

Research Team

JM

Joana M Mack, MD

Principal Investigator

University of Arkansas for Medical Sciences, Arkansas Children's Hospital

KJ

Kevin J Bielamowicz, MD,

Principal Investigator

University of Arkansas for Medical Sciences, Arkansas Children's Hospital

Eligibility Criteria

This trial is for people aged 2-80 with extracranial arteriovenous malformations (AVMs). Participants must be able to take oral medication, have a certain level of physical functioning, and normal organ function. Women who can get pregnant must use two forms of birth control and provide negative pregnancy tests. People with active cancer, severe allergies to cobimetinib components, recent infections or surgeries, heart problems, HIV, CNS hemorrhage history or those on certain medications are excluded.

Inclusion Criteria

I agree not to donate eggs or sperm during and for 3 months after the study.
I have an AVM outside the brain with measurable size and can provide a previous biopsy report or will undergo a biopsy.
Your platelet count should be at least 75 x 10^9 per liter of blood, and you should not have received a blood transfusion in the past 7 days.
See 11 more

Exclusion Criteria

I have been diagnosed with chronic HIV.
I haven't taken strong CYP3A4 drugs in the last 14 days.
I am currently pregnant or breastfeeding.
See 19 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cobimetinib for 21 days followed by 7 days off in a 28-day cycle, repeated for 12 cycles

12 months
Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Cobimetinib
Trial Overview The COBI-AVM study is testing the safety and effectiveness of cobimetinib in treating AVMs located outside the brain. It's an open-label trial where all participants know they're receiving the drug. The goal is to see how well it works and what side effects occur when used for this condition.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Investigational DrugExperimental Treatment1 Intervention
Cobimetinib will be administered at a maximal dose of 60 mg daily for 21 days on, then 7 days off, in a 28-Day treatment cycle for 12 cycles (approximately 12 months). Cobimetinib should be taken once daily at approximately the same time each day, and no later than 4 hours after the scheduled time. Cobimetinib can be taken with or without a meal. Cobimetinib tablets should never be chewed, cut, or crushed. Therapy may continue for up to 12 cycles provided the subject meets the criteria for starting subsequent cycles and does not meet any of the criteria for cobimetinib discontinuation. At least 7 days off cobimetinib (within +7 days) is required prior to starting a new treatment cycle.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials
500
Recruited
153,000+

Genentech, Inc.

Industry Sponsor

Trials
1,578
Recruited
569,000+
Ashley Magargee profile image

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway profile image

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a real-world study involving 95 patients with metastatic BRAF V600 mutated melanoma, the median overall survival (OS) was significantly higher for patients without brain metastases (21.6 months) compared to those with brain metastases (7.4 months).
The safety profile of cobimetinib/vemurafenib was consistent with previous studies, with high rates of adverse events (83.3% in patients without brain metastases and 87.8% in those with brain metastases), but no new safety concerns were identified.
Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS.Kähler, KC., Debus, D., Schley, G., et al.[2023]
Cobimetinib, when combined with vemurafenib, significantly improves tumor response rates and progression-free survival in metastatic melanoma patients with BRAF V600 mutations compared to vemurafenib alone.
While this combination therapy shows enhanced efficacy, it may also present higher toxicity compared to other treatments like dabrafenib and trametinib, indicating a need for careful management and potential combination with immune therapies for better long-term outcomes.
Cobimetinib and vemurafenib for the treatment of melanoma.Boespflug, A., Thomas, L.[2019]
In a study of 185 patients with advanced melanoma treated with cobimetinib and vemurafenib, the median overall survival was 16.1 months, indicating the effectiveness of this combination therapy in a real-world setting.
The safety profile was consistent with previous studies, with serious adverse events like increased CPK and retinal detachment occurring in 3% of patients, suggesting that while the treatment is effective, monitoring for these side effects is important.
Survival in adult patients with BRAFV600 mutation-positive advanced melanoma: a noninterventional ambispective study of patients with cobimetinib combined with vemurafenib during the French early access program: MELANIS study.Meyer, N., Pérol, D., Duval-Modeste, AB., et al.[2023]

References

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS. [2023]
Cobimetinib and vemurafenib for the treatment of melanoma. [2019]
Survival in adult patients with BRAFV600 mutation-positive advanced melanoma: a noninterventional ambispective study of patients with cobimetinib combined with vemurafenib during the French early access program: MELANIS study. [2023]
Cobimetinib Plus Vemurafenib: A Review in BRAF (V600) Mutation-Positive Unresectable or Metastatic Melanoma. [2019]
Phase I dose escalation trial of vandetanib with fractionated radiosurgery in patients with recurrent malignant gliomas. [2022]
A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors. [2019]
Cutaneous manifestations of anti-angiogenic therapy in oncology: Review with focus on VEGF inhibitors. [2022]
Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study. [2022]
Trametinib as a promising therapeutic option in alleviating vascular defects in an endothelial KRAS-induced mouse model. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Brain Vascular Malformation Consortium: Overview, Progress and Future Directions. [2021]
11.United Statespubmed.ncbi.nlm.nih.gov
Genetic Basis and Therapies for Vascular Anomalies. [2021]
12.United Statespubmed.ncbi.nlm.nih.gov
Molecular Biomarkers and Drug Targets in Brain Arteriovenous and Cavernous Malformations: Where Are We? [2022]
13.United Statespubmed.ncbi.nlm.nih.gov
Monitoring Arteriovenous Malformation Response to Genotype-Targeted Therapy. [2020]
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