Binimetinib With Docetaxel in Treating Patients With Previously Treated, Stage IV Non-small Cell Lung Cancer

NCT02451865 | Withdrawn Phase 1 DMC

• 3 other identifiers: 14-001595NCI-2015-00618Garon MEK162 NSCLC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the safety and best dose of binimetinib when given in combination with docetaxel in treating patients with previously treated, stage IV non-small cell lung cancer. Binimetinib and docetaxel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03

  Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.

  Up to 30 days post-treatment

• Incidence of dose-limiting toxicities, graded according to the CTCAE v4.03

  Side effects will be tabulated according to grade and will do sub-analysis based on patient demographic categories such as age and ECOG performance status.

  21 days

• Maximum tolerated dose of binimetinib in combination with docetaxel

  21 days

Secondary Outcomes (5)

• Biomarker analyses

  Up to 30 days post-treatment

• Mutations in KRAS and NRAS

  Up to 30 days post-treatment

• Objective tumor response rate (the rate of complete response or partial response), as defined by RECIST 1.1

  Up to 5 years

• Pharmacokinetic (PK) profile will assess binimetinib (MEK162) levels during treatment cycles

  On days 1 and 8 of course 1 and on day 1 of course 2

• Progression free survival

  Up to 5 years

Study Arms (1)

Treatment (binimetinib and docetaxel)

EXPERIMENTAL

Patients receive binimetinib PO BID on days 1-21 and docetaxel IV on day 21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease or better after completing 6 courses of binimetinib and docetaxel may continue receiving binimetinib PO BID in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Drug: Docetaxel; Other: Laboratory Biomarker Analysis

Interventions

Binimetinib DRUG

Given PO

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

Treatment (binimetinib and docetaxel)

Docetaxel DRUG

Given IV

Also known as: RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (binimetinib and docetaxel)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (binimetinib and docetaxel)

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
• A histologically or cytologically confirmed diagnosis of stage IV NSCLC
• Must have progressed on at least one prior line of platinum-based therapy for stage IV NSCLC (excluding docetaxel or mitogen activated protein kinase kinase \[MEK\] inhibitors)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Measurable disease defined by RECIST criteria
• Ability to provide adequate tissue from archival tumor specimen; confirmation of adequate tissue is required prior to enrollment
• In expansion cohort only: patient's kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status must be known prior to enrollment
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 g/dL without transfusions
• Platelets (PLT) \>= 100 x 10\^9/L without transfusions
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 1.5 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x ULN
• Creatinine =\< 1.5 mg/dL
• Left ventricular ejection fraction (LVEF) \>= 45% as determined by a multigated acquisition (MUGA) scan or echocardiogram, and QTc interval =\< 480ms
• Able to take and retain oral medications

You may not qualify if:

• 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 Gilbert syndrome
• Previous or concurrent malignancy within the last 3 years with the exception of adequately treated skin basal or squamous cell with adequate wound healing
• Prior therapy with a MEK-inhibitor or docetaxel for metastatic non-small cell lung cancer (docetaxel in the adjuvant setting will be allowed)
• Epidermal growth factor receptor (EGFR) mutant and/or anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearranged tumor
• Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following within 6 months of enrollment: myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting, symptomatic chronic heart failure, clinically significant cardiac arrhythmias and/or conduction (except atrial fibrillation and paroxysmal supraventricular tachycardia)
• Uncontrolled arterial hypertension despite appropriate medical therapy
• Known positive serology for human immunodeficiency virus (HIV), active hepatitis B, and/or active hepatitis C infection
• Neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy)
• Subjects planning on embarking on a new strenuous exercise regimen after first dose of study treatment that can result in significant increases in plasma CK levels
• Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption)
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to concerns regarding safety or compliance with clinical study procedures
• Patients who have undergone major surgery =\< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
• Pregnant or lactating women
• Women of child-bearing potential defined as all women physiologically capable of becoming pregnant who are unwilling to use highly effective methods of contraception throughout the study and 15 days after study drug discontinuation

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

binimetinib; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Edward Garon

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 22, 2015
• Study Start: June 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2019
• Last Updated: July 24, 2020

Record last verified: 2016-07

Locations

US (1)