Arteriovenous Malformations (Extracranial)Phase 2NCT05125471
Cobimetinib In Extracranial Arteriovenous Malformations (COBI-AVM Study)
A Phase 2 study testing Cobimetinib in people with Arteriovenous Malformations (Extracranial), run by University of Arkansas at 1 site in United States.
Trial summary
The purpose of this open-label study is to evaluate the safety and efficacy of cobimetinib in extracranial AVM. Read more about this study
- Who is it for?
- Ages 2 to 80 years
- Conditions the study is for
- Arteriovenous Malformations (Extracranial)
- What is being tested?
- Cobimetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 2022to 3 Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 2 years to 80 years of age
- Extracranial AVM with volumetric measurable disease AVM Tissue from a prior biopsy along with the corresponding pathology report will be required. If not available, a biopsy will be performed per standard of care
- Patient must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric or gastric tube
- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age
- ANC ≥ 0.75 x 109/L (unsupported/without growth factor stimulant in past 7 days) Platelet count ≥ 75 x 109/L (unsupported/without transfusion in past 7 days) Hemoglobin ≥ 8 g/dL (unsupported/without transfusion in past 7 days)
- Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m2 or serum creatinine based on age/gender as follows:
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- Age 2 < 6 years: Male 0.8; Female 0.8
- Age 6 to < 10 years: Male1; Female 1
- Age 10 to < 13 years: Male 1.2; Female 1.2
- Age 13 to < 16 years: Male 1.5; Female 1.4
- Age >/= 16 years: Male 1.7; Female 1.4
- AST and ALT ≤ 2.5 x upper limit of normal (ULN) for age Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x ULN for age
- Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram (ECHO) at Baseline, as determined by echocardiography within 21 days prior to study entry
- Female patients of childbearing potential (FOCBP) require a negative urine or serum pregnancy test at Baseline, within one week prior to the start of each cycle, at the End of Treatment (EOT) visit, and at the 28-Day Post-Treatment Safety Follow-Up (Safety Follow-Up) visit
- Female patients of childbearing potential and female partners of male patients who are pregnant or could become pregnant (i.e., females childbearing potential) must agree to follow the contraceptive requirements using two forms of effective contraceptive methods (one of which must be a barrier method) for the duration of the study treatment and for at least 3 months after the last dose of cobimetinib to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control
- Patients must also agree not to donate eggs (female patients) or sperm (male patients) during this study and for at least 3 months after the last dose of cobimetinib
Who cannot join
- Patients taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study entry, including but not limited to erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice, or St. John's Wort. Appendix A includes a list of other known CYP3A4 inducers and inhibitors that should be discontinued at least 14 days prior to initiation of cobimetinib and avoided during study participation, if reasonable alternatives exist
- Completion of previous chemotherapy, immunotherapy, or targeted therapy for extracranial AVM with resolution of all associated toxicity to ≤ Grade 1 (except for alopecia and ototoxicity, which do not need to be resolved ≤ Grade 1) at least 28 days prior to study entry (except if otherwise specified below). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to study entry. If, after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately
- Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of cobimetinib or a short-acting hematopoietic growth factor within 7 days prior to study entry
- Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study entry
- Corticosteroid therapy < 0.5 mg/kg/day averaged during the month prior to study entry is permissible but must be discontinued 14 days prior to study entry
- Active malignancy or history of secondary malignancy
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- History of severe hypersensitivity reactions to components of cobimetinib
- Refractory nausea and vomiting, malabsorption, external biliary shunt
- Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to study entry that has not completely resolved
- Major surgical procedure or significant traumatic injury within 28 days prior to study entry, or anticipation of the need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within 14 days of study entry (provided the wound has healed)
- History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
- History of pneumonitis
- Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded
- Any other disease, metabolic or psychological dysfunction, physical examination or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the Investigator's judgement contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications
- Clinically significant cardiac arrhythmias or unstable arrhythmia including bradyarryhthmias and/or patients who require anti-arrhythmic therapy (with the exception of beta-blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
- Unstable angina, or new-onset angina within 3 months prior to initiation of cobimetinib
- Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
- Myocardial infarction within 3 months prior to initiation of cobimetinib
- Known chronic human immunodeficiency virus (HIV)
- History of ≥ Grade 2 central nervous system (CNS) hemorrhage or history of any CNS hemorrhage within 28 days of study entry
- Female patients who are pregnant or lactating. Pregnant or lactating women will not be enrolled in this study because there is no available information regarding human fetal or teratogenic toxicities.
- Patient has received treatment with investigational therapy within 4 weeks prior to initiation of cobimetinib.
Trial locations and contacts
1 site in 1 country.
United States1 site
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
About this study
Official title: COBI-AVM Study - Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib In Extracranial Arteriovenous Malformations (AVM)
The purpose of this open-label study is to evaluate the safety and efficacy of cobimetinib in extracranial AVM.
Read the detailed description
After being informed of the study and potential risks, all patients giving informed consent will go undergo a screening period to determine eligibility for study entry. Patients who meet the eligibility requirements will be given cobimetinib to take by mouth once daily at the same time each day for 21 days and then have 7 days with no treatment. Patients will receive cobimetinib as a tablet (adult) or as a liquid (child).
- Being tested
- Cobimetinib
- Medical subject headings
- Arteriovenous Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobimetinibDrug
Also called Cotellic
Adult dosing (>/= 18 years old) will be 60 mg orally once daily (tablet formulation); Pediatric dosing (<18 years old) will be 1 mg/kg/dose (maximum 60 mg per dose) orally once daily (oral suspension formulation).
| Study group | Role | What they receive |
|---|---|---|
| Investigational Drug | Experimental | 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. Receives: Drug: Cobimetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response (CR) or partial response (PR) rate compared to Baseline
Response will be determined by a blinded, centralized review of volumetric MRI. Partial response is defined as a >/= 20% reduction in target extracranial AVM volume
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2021
- Study start26 Jul 2022
- Primary completion3 Sep 2025
- Study completion3 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arteriovenous Malformations (Extracranial)Studies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Cobimetinib will be given orally at the recommended phase 2 dose (RP2D).
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Joana M Mack, MD, Principal investigator, University of Arkansas for Medical Sciences, Arkansas Children's HospitalKevin J Bielamowicz, MD,, Principal investigator, University of Arkansas for Medical Sciences, Arkansas Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05125471
- Sponsor's protocol ID
- 261983
- Status last verified
- Jun 2025
- First submitted
- 12 Nov 2021
- Last updated
- 10 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COBI-AVM Study - Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib In Extracranial Arteriovenous Malformations (AVM)
- ClinicalTrials.gov ID
- NCT05125471
- Acronym / sponsor ID
- 261983
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 26 Jul 2022 (actual)
- Primary completion
- 3 Sep 2025 (actual)
- Study completion
- 3 Sep 2025 (actual)
- First posted
- 18 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this open-label study is to evaluate the safety and efficacy of cobimetinib in extracranial AVM.
Detailed description
After being informed of the study and potential risks, all patients giving informed consent will go undergo a screening period to determine eligibility for study entry. Patients who meet the eligibility requirements will be given cobimetinib to take by mouth once daily at the same time each day for 21 days and then have 7 days with no treatment. Patients will receive cobimetinib as a tablet (adult) or as a liquid (child).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Cobimetinib will be given orally at the recommended phase 2 dose (RP2D).
| Arm | Type | Receives |
|---|---|---|
| Investigational Drug | Experimental | Drug: CobimetinibCobimetinib 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. |
Who may qualify
- Ages
- 2 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- 2 years to 80 years of age
- Extracranial AVM with volumetric measurable disease AVM Tissue from a prior biopsy along with the corresponding pathology report will be required. If not available, a biopsy will be performed per standard of care
- Patient must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric or gastric tube
- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age
- ANC ≥ 0.75 x 109/L (unsupported/without growth factor stimulant in past 7 days) Platelet count ≥ 75 x 109/L (unsupported/without transfusion in past 7 days) Hemoglobin ≥ 8 g/dL (unsupported/without transfusion in past 7 days)
Key exclusion criteria (22 listed)
- Patients taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study entry, including but not limited to erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice, or St. John's Wort. Appendix A includes a list of other known CYP3A4 inducers and inhibitors that should be discontinued at least 14 days prior to initiation of cobimetinib and avoided during study participation, if reasonable alternatives exist
- Completion of previous chemotherapy, immunotherapy, or targeted therapy for extracranial AVM with resolution of all associated toxicity to ≤ Grade 1 (except for alopecia and ototoxicity, which do not need to be resolved ≤ Grade 1) at least 28 days prior to study entry (except if otherwise specified below). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to study entry. If, after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately
- Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of cobimetinib or a short-acting hematopoietic growth factor within 7 days prior to study entry
- Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study entry
- Corticosteroid therapy < 0.5 mg/kg/day averaged during the month prior to study entry is permissible but must be discontinued 14 days prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobimetinibAlso: CotellicAdult dosing (>/= 18 years old) will be 60 mg orally once daily (tablet formulation); Pediatric dosing (<18 years old) will be 1 mg/kg/dose (maximum 60 mg per dose) orally once daily (oral suspension formulation). | Drug | Investigational Drug |
Primary outcome
Complete response (CR) or partial response (PR) rate compared to Baseline
Time frame: Through study completion, an average of 1 year
Response will be determined by a blinded, centralized review of volumetric MRI. Partial response is defined as a >/= 20% reduction in target extracranial AVM volume
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
- Individual participant dataSharing planned: No
Related trials for Arteriovenous Malformations (Extracranial)
RecruitingObservational study
RSSearch Patient Registry-Long Term Study of Use of SRS/SBRT
Neoplasms, Arteriovenous Malformation of Central Nervous System
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joana M Mack, MD principal investigator
University of Arkansas for Medical Sciences, Arkansas Children's Hospital
Kevin J Bielamowicz, MD, principal investigator
University of Arkansas for Medical Sciences, Arkansas Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cobimetinib in people with Arteriovenous Malformations (Extracranial), run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (CR) or partial response (PR) rate compared to Baseline (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2025.