An Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-mutant Melanoma Brain Metastasis

Study Purpose

This is a multicenter, randomized open-label Phase 2 study to assess the safety, efficacy and pharmacokinetic (PK) of 2 dosing regimens of encorafenib + binimetinib combination in patients with BRAFV600-mutant melanoma with brain metastasis. Approximately 100 patients will be enrolled, including 9 patients in a Safety Lead-in of the high-dose treatment arm. After a Screening Period, treatment will be administered in 28-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent, start of subsequent anticancer therapy, death.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Key

Inclusion Criteria:

- Histologically confirmed diagnosis of cutaneous melanoma with metastases to the brain.

- Presence of B-RAF proto-oncogene, V600 mutant (BRAFV600) mutation in tumor tissue previously determined by a local PCR or NGS-based assay at any time prior to Screening or by a central laboratory during Screening.

- Must have at least 1 parenchymal brain lesion ≥ 0.5 cm and ≤ 4 cm, defined as a magnetic resonance imaging (MRI) contrast-enhancing lesion that may be accurately measured in at least 1 dimension.

(Measurable intracranial lesions that have been previously irradiated and have not been shown to be progressing following irradiation should not be considered as target lesions).

- Patients may have received the following prior therapies: 1.

Safety Lead-in, Phase 2 Randomized , Phase 2 Arm A Cohort 1: May have received prior local therapy for brain metastases including but not restricted to brain surgery, whole brain radiotherapy, stereotactic radiotherapy or stereotactic radiosurgery. Multiple local (brain) therapies or combinations of local therapies are allowed. For patients receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For patients receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated. 2. Phase 2 Arm A Cohort 2: Received no prior local therapy (e.g., brain surgery, craniotomy, SRS or SRT) for brain metastases. 3. All patients (Safety Lead-In and Phase 2): May have received prior immunotherapy. 4. All patients (Safety Lead-In and Phase 2): If receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to first dose of study treatment (up to a total daily dose of 4mg of dexamethasone or equivalent).

- An Eastern Cooperation Oncology Group Performance Status (ECOG PS) of 0 or 1 and Karnofsky score ≥ 80.

- Adequate bone marrow, organ function and laboratory parameters.

Key

Exclusion Criteria:

- Patients with symptomatic brain metastasis.

- Uveal or mucosal melanoma.

- History of or current leptomeningeal metastases.

- Treatment with SRS or craniotomy within 14 days prior to start of study treatment, or treatment with whole-brain radiation within 28 days prior to study treatment.

Patients who received local therapy should have complete recovery with no neurological sequelae.

- Either of the following: 1.

Radiation therapy to non-brain visceral metastasis within 2 weeks prior to start of study treatment; 2. Continuous or intermittent small-molecule therapeutics or investigational agents within 5 half-lives of the agent (or within 4 weeks prior to start of study treatment, when half-life is unknown).

- Patients treated in the adjuvant setting with BRAF or MEK inhibitor(s) < 6 months prior to enrollment.

Patients who received BRAF or MEK inhibitors in the metastatic setting are excluded.

- Patient has not recovered to ≤ Grade 1 from toxic effects of prior therapy before starting study treatment.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03911869
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Pfizer
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Pfizer CT.gov Call Center
Principal Investigator Affiliation	Pfizer
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Belgium, Canada, Italy, Netherlands, New Zealand, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Metastases
Study Website:	View Trial Website

Arms & Interventions

Arms

Experimental: Standard Dose Arm

Patients in the standard-dose treatment arm will receive encorafenib and binimetinib in 28-day cycles. 450 mg encorafenib orally once a day (QD) 45 mg binimetinib orally twice a day (BID) Patients who are able to tolerate the standard dose during the first 4 weeks of treatment (Cycle 1) should be dose-escalated to 600 mg encorafenib QD plus 45 mg binimetinib BID provided they meet protocol-defined criteria.

Experimental: High Dose Arm

Patients in the high-dose treatment arm will receive encorafenib and binimetinib in 28-day cycles. 300 mg encorafenib orally twice a day (BID) 45 mg binimetinib orally twice a day (BID)

Interventions

Drug: - encorafenib

taken orally

Drug: - binimetinib

taken orally

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Encinitas, California

Status

Not yet recruiting

Address

California Cancer Associates for Research and Excellence

Encinitas, California, 92024

Site Contact

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