AzTrials
AzTrials

Advanced BRAF Mutant CancersPhase 1/2NCT03843775

A Study of Binimetinib and Encorafenib in Advanced BRAF Mutant Cancers

A Phase 1/2 study testing Binimetinib and Encorafenib in people with Advanced BRAF Mutant Cancers, run by Memorial Sloan Kettering Cancer Center at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this trial is to test the safety and efficacy of an innovative combination aimed to more profoundly inhibit ERK signaling in tumors. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced BRAF Mutant Cancers
What is being tested?
Binimetinib and Encorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
4 sitesUnited States
Study dates
14 Feb 2019to 2 Sep 2023
Phase
Phase 1/2
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

  • Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements
  • Age ≥ 18 years at the time of informed consent
  • Metastatic or advanced-stage malignant tumors confirmed histologically for whom no standard therapy is considered to be appropriate by the investigator
  • Patients must have at least one other lesion that is measurable by RECIST criteria.
  • Patient's tumor must harbor an activating BRAF mutation (listed in Table 4 or approved by the study Principal Investigator) or a fusion involving the kinase domain of BRAF
  • Mechanistically validated activating non-V600 BRAF mutants
Show all 36Show fewer
  • P367L/S
  • G464V/E
  • G469A/V/R
  • L485W
  • N486_A489delinsK
  • N486_P490del
  • E586K
  • L597Q/V/S
  • T599TT/TS
  • T599I/K
  • V600_K601delinsE
  • K601E/N/T
  • K601_S602delinsNT
  • BRAF kinase duplication
  • Fusions involving BRAF kinase domain
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  • Adequate bone marrow, organ function and laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Hemoglobin (Hgb) ≥ 8 g/dL with or without transfusions
  • Platelets (PLT) ≥ 75 x 109/L without transfusions
  • AST and/or ALT ≤ 2.5 × upper limit of normal (ULN); patient with liver metastases ≤ 5 ×ULN
  • Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL (Note: Patients who have a total bilirubin level > 1.5 x ULN will be allowed if their indirect bilirubin level is ≤ 1.5 x ULN)
  • Serum Creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50 mL/min at screening
  • Adequate cardiac function:
  • left ventricular ejection fraction (LVEF) ≥ 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
  • QTc interval ≤ 480 ms (preferably the mean from triplicate ECGs)
  • Able to take oral medications
  • Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up)
  • Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through 30 days after the last dose of study drug/treatmentif of childbearing potential (Note: Permitted contraception methods listed in Section 9.3 should be communicated to the patients and their understanding confirmed. For females of childbearing potential, the pregnancy test result must be negative at screening.)
  • Males must agree to take appropriate precautions to avoid fathering a child from screening through 90 days following the end of therapy. (Note: Permitted contraception methods listed in Section 9.3 should be communicated to the patients and their understanding confirmed.)

Who cannot join

  • Any symptomatic brain metastasis (Note: Patients previously treated or untreated for this condition who are asymptomatic in the absence of corticosteroid and antiepileptic therapy are allowed. Brain metastases must be stable for ≥ 4 weeks, with imaging (e.g., magnetic resonance imaging [MRI] or computed tomography [CT]) demonstrating no current evidence of progressive brain metastases at screening.)
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
  • Leptomeningeal disease
  • Previous or concurrent malignancy within 2 years of study entry, with the following exceptions: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, early stage breast cancer, or other noninvasive or indolent malignancy
  • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening
Show all 17Show fewer
  • Symptomatic chronic heart failure (i.e. Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
  • Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg, despite current therapy.
  • Known positive serology for HIV (Human Immunodeficiency Virus), active hepatitis B, and/or active hepatitis C infection
  • Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
  • History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
  • Note: Patients with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks. Note: Patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled.Concurrent neuromuscular disorder that is associated with the potential of elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  • Any other condition that would, in the Investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medications, social/psychological issues, etc.
  • Patients who have undergone surgery ≤ 3 weeks prior to starting study drug or who have not yet recovered from side effects of such procedure
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
  • Medical, psychiatric, cognitive, or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
  • Prior treatment with any RAF, MEK, or ERK inhibitors (such as vemurafenib, dabrafenib, encorafenib; trametinib, cobimetinib, binimetinib, selumetinib; or BVD-523, respectively)

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Memorial Sloan Kettering Cancer Center @ Suffolk (Limited protocol activity)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I/II Study of Binimetinib With Encorafenib in Patients With Non-V600 Activating BRAF Mutant Advanced Malignancies

The goal of this trial is to test the safety and efficacy of an innovative combination aimed to more profoundly inhibit ERK signaling in tumors.

Being tested
Binimetinib, Encorafenib
Keywords
Binimetinib, Encorafenib, 18-547

What participants receive

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

  • BinimetinibDrug

    Also called MEK162 or ARRY-438162

    Dose level 1 binimetinib 45 mg PO BID. Dose level 2 binimetinib 60 mg oral BID

  • EncorafenibDrug

    Also called LGX818

    encorafenib 450 mg oral QD

Study groups in NCT03843775
Study groupRoleWhat they receive
Binimetinib and EncorafenibExperimentalPatients will be initially enrolled to the approved dose of encorafenib 450 mg oral QD and binimetinib 45 mg PO BID, dose level 1. If confirmed this dose level is safely tolerated in the study population, we will then escalate treatment to dose level 2 with the novel dosing regimen of encorafenib 450 mg oral QD continuous and binimetinib 60 mg oral BID 21 days on/7 days off.
Receives: Drug: Binimetinib; Drug: Encorafenib

What is being measured

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

  1. Dose-limiting Toxicities (DLTs)

    National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5,

    Measured: 1 year

  2. Objective Response Rate (Phase II)

    Per RECIST Version 1.1

    Measured: 1 year

Timeline

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

  1. First posted18 Feb 2019
  2. Study start14 Feb 2019
  3. Primary completion2 Sep 2023
  4. Study completion2 Sep 2023

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This phase I/II study consists of a Phase I part followed by an efficacy analysis (Phase II) of the dosing schedule deemed safe in patients with advanced cancer with activating non-V600 BRAF mutant tumors. As patients in the phase I part of the start will start at the lower dose level 1, they will not be included in the stage one efficacy cohort.
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03843775
Sponsor's protocol ID
18-547
Status last verified
Oct 2024
First submitted
15 Feb 2019
Last updated
21 Oct 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Publications

  • Rajkumar S, Berry D, Heney KA, Strong C, Ramsay L, Lajoie M, Alkallas R, Nguyen TT, Thomson C, Ahanfeshar-Adams M, Dankner M, Petrella T, Rose AAN, Siegel PM, Watson IR. Melanomas with concurrent BRAF non-p.V600 and NF1 loss-of-function mutations are targetable by BRAF/MEK inhibitor combination therapy. Cell Rep. 2022 Apr 5;39(1):110634. doi: 10.1016/j.celrep.2022.110634.

    PubMed 35385748

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Binimetinib and Encorafenib in people with Advanced BRAF Mutant Cancers, run by Memorial Sloan Kettering Cancer Center at 4 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 36 inclusion and 17 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 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 21 Oct 2024). 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?

Dose-limiting Toxicities (DLTs) (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT03843775, which also lists 1 linked publication.

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 21 Oct 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in