A study of binimetinib and encorafenib in patients aged 12 to 17 with a specific type of melanoma (BRAF V600-mutant melanoma) that cannot be completely removed by surgery or that has spread to other areas in the body.
- Conditions
- nresectable or metastatic BRAF V600-mutant melanomaMedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001946-32-IT
- Lead Sponsor
- ARRAY BIOPHARMA INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 18
1.Written informed consent provided by the patient or, for patients less than the local age of legal consent, by their legally authorized guardian or representative. When appropriate, pediatric patients will be included in all discussions regarding participation in the trial and their assent will be obtained and documented.
2. Male or female 12 to < 18 years of age at the time of consent/assent.
3. Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer Stage IIIB, IIIC, or IV.
4. Presence of BRAF V600E or V600K mutation in tumor tissue as determined by a local or central laboratory.
5. Evidence of at least one evaluable lesion (measurable or nonmeasurable) as detected by radiological or photographic methods based on RECIST v1.1.
6. Adequate cardiac function:
a. Left ventricular ejection fraction = 50% as determined by ECHO or MUGA scan and above the institutional lower limit of normal;
b. Triplicate average baseline QTcF value = 450 ms.
7. Adequate bone marrow, organ function, and laboratory parameters:
a. Absolute neutrophil count = 1.5 × 109/L;
b. Hemoglobin = 9 g/dL with or without transfusions;
c. Platelets = 75 × 109/L without transfusions;
d. Aspartate aminotransferase and/or alanine aminotransferase = 2.5 × upper limit of normal (ULN); in patients with liver metastases = 5 × ULN;
e. Total bilirubin = 1.5 × ULN NOTE: Patients with documented Gilbert syndrome or hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled followingdiscussion and agreement with the Array Medical Monitor
f. Creatinine = 1.5 × institutional ULN for age, or calculated creatinine
clearance = 70 mL/min/1.73 m2 (following Schwartz formula).
8. Adequate performance status at Screening:
a. Patients < 16 years old: Lansky Performance Scale score = 80
b. Patients 16 to 17 years old: Karnofsky Performance Scale score = 80
9. Female patients of childbearing potential must agree to take appropriate precautions to avoid pregnancy from screening through 8 weeks following end of therapy and must have a negative pregnancy test at Screening and predose at Day 1.
10. Males must agree to take appropriate precautions to avoid fathering a child from Screening through 90 days following end of therapy.
11.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Presence of BRAF wt or indeterminate melanoma in tumor tissue as determined by local and central laboratory.
2. Known sensitivity or contraindication to any component of study treatment (binimetinib and encorafenib), or their excipients
3.Uveal or mucosal melanoma.
4.Brain metastases that are uncontrolled or symptomatic, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug.
5.History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes, but not including thromboses related to indwelling vascular access devices).
6.Prior therapy with a BRAF inhibitor (e.g., dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., trametinib, cobimetinib).
7.Impaired cardiovascular function or clinically significant cardiovascular disease, including any of the following:
a.History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to screening,
b.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.
8.Concurrent neuromuscular disorder associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, spinal muscular atrophy).
9.Impairment of gastrointestinal function (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome such as that due to small bowel resection).
10.Uncontrolled arterial hypertension despite medical treatment.
11.Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
12.Known active hepatitis B and/or active hepatitis C infection.
13.Patients who have undergone major surgery or radiotherapy = 2 weeks prior to starting study treatment or who have not recovered from side effects of such procedure.
14.Pregnant or nursing (lactating) females.
15.Receipt of non-topical medication known to be a strong inhibitor or strong inducer of cytochrome P450 (CYP) 3A4 within 3 days prior to Screening.
16.Medical, psychiatric, cognitive or other conditions that may compromise the patient’s ability to understand the patient information, give informed consent/assent, comply with the study protocol or complete the study.
17.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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method