Intermittent LGX818 and MEK162 in Treating Patients With Metastatic Melanoma Who Have BRAFV600 Mutations

NCT02263898 | Withdrawn Phase 2 DMC

• 3 other identifiers: 14-000616NCI-2014-01971P01CA168585
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies intermittent dosing of BRAF inhibitor LGX818 (encorafenib) and MEK inhibitor MEK 162 (binimetinib) in treating patients with melanoma that has spread to other parts of the body (metastatic) and have a BRAF V600 mutation. LGX818 and MEK162 may stop the growth of tumor cells by blocking different enzymes needed for cell growth. Giving LGX818 and MEK162 with breaks between each course (intermittently) may help delay the time when tumors become resistant to the drugs.

Conditions

Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• PFS rate

  1 year

Study Arms (1)

Treatment (LGX818, MEK162)

EXPERIMENTAL

Patients receive LGX818 PO QD and MEK162 PO BID continuously for 8 weeks followed by intermittent dosing in subsequent cycles (3 weeks off therapy, 5 weeks on therapy). Cycles repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Raf kinase inhibitor LGX818; Drug: binimetinib; Other: laboratory biomarker analysis

Interventions

Raf kinase inhibitor LGX818 DRUG

Given PO

Also known as: LGX818

Treatment (LGX818, MEK162)

binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK inhibitor ARRY-438162, MEK162

Treatment (LGX818, MEK162)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (LGX818, MEK162)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Histologically confirmed diagnosis of metastatic melanoma with the presence of the B-Raf proto-oncogene, serine/threonine kinase (BRAFV600) mutation
• Eastern Cooperative Oncology Group (ECOG) performance status \< 3
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 g/dL without transfusions
• Platelets (PLT) \>= 90 x 10\^9/L without transfusions
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN); patient with liver metastases =\< 5 x ULN
• Total bilirubin =\< 2 x ULN, or \< 5 ULN if Gilbert’s disease
• Creatinine =\< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) \>= 50 mL/min
• Left ventricular ejection fraction (LVEF) \>= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram (ECHO)
• Corrected QT (QTc) interval =\< 480 ms
• 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)
• Negative serum beta (β) human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within 72 hours prior to first dose

You may not qualify if:

• Prior exposure to BRAF or MEK inhibitors
• Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; however, patient treated with stereotactic radiotherapy, whole brain radiation or surgery are eligible if patient remained without evidence of CNS disease progression \>= 4 weeks; patients must be off corticosteroid therapy for \>= 2 weeks
• History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• History of retinal degenerative disease
• History of Gilbert’s syndrome
• 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,
• Symptomatic chronic heart failure, 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 arterial hypertension despite medical treatment
• Known positive serology for HIV (human immunodeficiency virus), active hepatitis B, and/or active hepatitis C infection
• Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
• Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• Patients taking non-topical medication known to be a strong inhibitor of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); however patients who either discontinue their treatment or switch to another medication at least three days prior to randomization are eligible
• Any other condition that would, in the Investigator’s judgment, 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 medication, social/psychological issues, etc.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

encorafenib; binimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Antoni Ribas

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: October 13, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2020
• Last Updated: July 27, 2020

Record last verified: 2016-12

Locations

US (1)