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Active Melanoma Brain MetastasesPhase 2CoBRIM-BNCT02230306

Phase II Study of Cobimetinib in Combination With Vemurafenib in Active Melanoma Brain Metastases

A Phase 2 study testing Cobimetinib and Vemurafenib in people with Active Melanoma Brain Metastases, run by Melissa Burgess, MD at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to evaluate the effectiveness of the combination of vemurafenib with cobimetinib in patients with active melanoma brain metastases. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Active Melanoma Brain Metastases
What is being tested?
Cobimetinib and Vemurafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
6 sitesUnited States
Study dates
Feb 2015to Mar 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent
  • Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600-mutation
  • Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory
  • At least one measurable intracranial target lesion for which all of the following criteria are met:
  • previously untreated or progressive according to RECIST 1.1 (equal to or greater than 20% increase in longest diameter on baseline scan) after previous local therapy (SRS and/or craniotomy)
  • immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy (SRS and/or craniotomy)
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  • largest diameter of ≥ 0.5cm but ≤ 4 cm as determined by contrast-enhanced MRI
  • Prior therapies for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy will be allowed but prior BRAF or MEK not allowed
  • ECOG PS 0-2
  • Life expectancy >12 weeks
  • Age 18 years or older
  • Adequate bone marrow function as indicated by the following:
  • ANC > 1500/µL
  • Platelets ≥ 100,000/µL
  • Hemoglobin > 9 g/dL
  • Adequate renal function, as indicated by creatinine =/< 1.5 x the upper limit of normal (ULN)
  • Adequate liver function, as indicated by bilirubin =/< 1.5 x ULN
  • AST or ALT < 3 x ULN (patients with documented liver metastases: AST and/or ALT =/< 5 x ULN)
  • Able to swallow pills
  • Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year
  • Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

Who cannot join

  • Active infection
  • Prior therapy with BRAFi and/or MEKi
  • Leptomeningeal disease
  • Symptomatic brain metastases requiring immediate local interventions such as craniotomy or SRS
  • Increasing corticosteroid dose in 7 days prior to administration of first dose of study drug. Symptomatic patients that have stable or decreasing corticosteroid use in the past 7 days will be allowed
  • Current use of therapeutic warfarin
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  • Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) [NCI, 2009] Grade 2 or higher from previous anti-cancer therapy, except alopecia
  • Conditions that will interfere significantly with the absorption of drugs
  • Inability to undergo MRI secondary to metal, claustrophobia, Gadolinium Contrast allergy
  • Pregnant, lactating, or breast feeding women
  • Prior radiation therapy within the last 14 days
  • Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • Unwillingness or inability to comply with study and follow-up procedures
  • The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:
  • St. John's wort or hyperforin
  • Grapefruit juice
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, Retinal Vein Occlusion (RVO), or neovascular macular degeneration
  • Uncontrolled glaucoma with intra-ocular pressures > 21mmHg
  • Serum cholesterol ≥ Grade 2
  • Hypertriglyceridemia ≥ Grade 2
  • Hyperglycemia (fasting) ≥ Grade 2
  • History of clinically significant cardiac dysfunction, including the following:
  • Current unstable angina
  • Current symptomatic congestive heart failure of NYHA class 2 or higher
  • History of congenital long QT syndrome or mean QTcF > 450 msec at baseline or uncorrectable electrolyte abnormalities
  • Uncontrolled hypertension ≥ Grade 2 (patients with a history hypertension controlled with anti-hypertensives to ≤ Grade 1 are eligible)
  • Left ventricular ejection fraction (LVEF) below 50%
  • Uncontrolled Arrhythmias
  • Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Mohammed Milhem, MD

    Iowa City, Iowa, 52242

  • Harriet Kluger

    New Haven, Connecticut, 06510

  • Anna Pavlick, MD

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Ravi Amaravadi, MD

    Philadelphia, Pennsylvania, 19104

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

The purpose of this study is to evaluate the effectiveness of the combination of vemurafenib with cobimetinib in patients with active melanoma brain metastases.

Being tested
Cobimetinib, Vemurafenib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobimetinibDrug

    60mg once a day; will be taken on days 1-21 of each 28 day treatment cycle; will be taken in combination with Vemurafenib;

  • VemurafenibDrug

    Also called Zelboraf

    960mg twice a day; 28 day treatment cycle; will be taken in combination with Cobimetinib;

Study groups in NCT02230306
Study groupRoleWhat they receive
Cobimetinib in Combination with VemurafenibExperimentalVemurafenib (960 mg twice a day) will be taken on Days 1 - 28 of each 28-day treatment cycle. The first dose of vemurafenib should be taken in the morning, and the second dose should be taken in the evening. Vemurafenib can be taken with or without a meal and should be taken with a glass of water. Cobimetinib (60 mg once a day) will be taken on Days 1 - 21 of each 28-day treatment cycle. The cobimetinib tablet should be taken at approximately the same time each day in the morning with the vemurafenib dose, but no later than 4 hours after the scheduled time. Cobimetinib can be taken with or without a meal and should never be chewed, cut, or crushed and should be taken with a glass of water.
Receives: Drug: Cobimetinib; Drug: Vemurafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Intracranial Response (OIRR)

    Change in overall size of the sum of diameters from baseline of up to 5 intracranial target lesions in response to study treatment, achieved by individual patients.

    Measured: Until disease progression, less than or equal to 5 years.

Secondary outcomes (7)

  1. Overall Response

    Response to study treatment achieved by individual patients as indicated by an overall change in size of the sum of diameters from baseline of up to 5 intracranial target lesions and up to 5 extracranial target lesions.

    Measured: Until disease progression, less than or equal to 5 years.

  2. Progression-free Survival (PFS)

    Time (number of months) from first documented evidence of overall Complete Response (CR) or Partial Response (PR) until time of first documented disease progression or death due to any cause (for individual patients). Progression as defined by RECIST 1.1 (Response Evaluation Criteria In Solid Tumors) is a ≥ 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm.

    Measured: Up to 5 years

  3. Overall Survival (OS)

    Number of months of survival for individual patients.

    Measured: Up to 5 years

  4. Duration of Response

    Change in relative apparent diffusion coefficient (rADC) as measured by MRI as early predictor of response value/result for each patient

    Measured: Until disease progression, less than or equal to 5 years.

  5. Immune Modulation in Peripheral Blood

    Measured: Up to 5 years

  6. Early Markers of Progression in Peripheral Blood

    Measured: Up to 5 years

  7. Health-related Quality of Life as Measured by The Functional Assessment of Cancer Therapy (FACT) - Brain (FACT-Br)

    The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is used to measure general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 scales. The brain subscale is usually used along with the core (general) questionnaire that includes 27 items. The measure yields information about total QOL, as well as information about the dimensions of physical well-being, social/family well-being, emotional well being, functional well-being, and disease-specific concerns. Patients rate all 5 items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher QOL. Items are totaled to produce the following subscales, along with an overall QOL score: physical well-being (7 items); social/family well-being (7 items); emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items). Scoring range is 0-200.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2014 (estimated)
  2. Study startFeb 2015
  3. Primary completionMar 2016
  4. Study completionMar 2016

Why it stopped: closed due to slow accrual

Resources

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
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02230306
Sponsor's protocol ID
13-123
Other IDs
ML29155
Acronym
CoBRIM-B
Status last verified
Sep 2017
First submitted
27 Aug 2014
Last updated
12 Oct 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cobimetinib and Vemurafenib in people with Active Melanoma Brain Metastases, run by Melissa Burgess, MD at 6 sites 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 21 inclusion and 29 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: stopped early, as of the sponsor's last update on 12 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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?

Yes. Results are posted in the registry (first posted 12 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Intracranial Response (OIRR) (time frame: Until disease progression, less than or equal to 5 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02230306.

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 12 Oct 2017.

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