A 2-part phase III randomized, open label, multicenter study of LGX818 plus MEK162 versus vemurafenib and LGX818 monotherapy in patients with unresectable or metastatic BRAF V600 mutant melanoma
- Conditions
- Melanoma10027656
- Registration Number
- NL-OMON53071
- Lead Sponsor
- Array Biopharma Inc. (a wholly owned subsidiary of Pfizer Inc.)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 50
1. Male or female patient, age >= 18 years;
2. Histologically confirmed diagnosis of locally advanced, unresectable or
metastatic cutaneous melanoma or unknown primary melanoma AJCC Stage IIIB, IIIC
or IV
3. Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to
enrollment, as determined by a sponsor designated central laboratory(ies);
4. Naïve untreated patients or patients who have progressed on or after prior
first-line immunotherapy for unresectable locally advanced or metastatic
melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any
other immunotherapy, radiotherapy, chemotherapy), except the administration of
BRAF or MEK inhibitors.
5. Evidence of at least one measurable lesion as detected by radiological or
photographic methods , 6. ECOG performance status of 0 or 1
7. Adequate bone marrow, organ function and laboratory parameters:
7.1. Absolute neutrophil count (ANC) >= 1.5 x 109/L,
7.2. Hemoglobin (Hgb) >= 9 g/dL without transfusions,
7.3. Platelets (PLT) >= 100 x 109/L without transfusions,
7.4. AST and/or ALT <= 2.5 × upper limit of normal (ULN); patient with liver
metastases <= 5 ×ULN,
7.5. Total bilirubin <= 2 × ULN,
7.6. Creatinine <= 1.5 mg/dL, or calculated creatinine clearance (determined as
per Cockcroft-Gault) >= 50mL/min;
8. Adequate cardiac function:
8.1. left ventricular ejection fraction (LVEF) >= 50% as determined by a
multigated acquisition (MUGA) scan or echocardiogram,
8.2. QTc interval <= 480 ms;
9. Negative serum β HCG test
1. Any untreated central nervous system (CNS) lesion. However, patient treated
with radiotherapy or surgery are eligible if patient remained without evidence
of CNS disease progression >= 4 weeks. Patients must be off corticosteroid
therapy for >= 3 weeks.
2. Uveal and mucosal melanoma
3. History of leptomeningeal metastases;
4. History or current evidence of retinal vein occlusion or current risk
factors for RVO, 6. History of allogeneic bone marrow transplantation or organ
transplantation;
7. Previous or concurrent malignancy with the following exceptions:
• adequately treated basal cell or squamous cell carcinoma of the skin
• in situ carcinoma of the cervix, treated curatively and without evidence of
recurrence for at least 3 years prior to the study,
• or other solid tumor treated curatively, and without evidence of recurrence
for at least 3 years prior to study entry;
8. Any previous systemic chemotherapy treatment, extensive radiotherapy or
investigational agent other than immunotherapy, or patients who have
received more than one line of immunotherapy for locally advanced
unresectable or metastatic melanoma., 9. Impaired cardiovascular function or
clinically significant cardiovascular diseases
10. Uncontrolled arterial hypertension despite medical treatment;
11. Known positive serology for HIV, active hepatitis B, and/or active
hepatitis C infection;
12. Patients who have neuromuscular disorders that are associated with elevated
CK
13. Impairment of gastrointestinal function or gastrointestinal disease
14. Pregnant or nursing (lactating) women
15. Women of child-bearing potential, unless they are using highly effective
methods of contraception throughout the study and for 8 weeks after study drug
discontinuation.
16. Sexually active males unless they use a condom during intercourse while
taking the drug and for 8 weeks after stopping treatment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS, defined as the time from the date of randomization to the date of the<br /><br>first documented disease progression or death due to any cause, whichever<br /><br>occurs first.<br /><br><br /><br>PFS will be determined based on tumor assessment (RECIST version 1.1 criteria)<br /><br>as per BIRC and survival information.<br /><br>The local Investigator*s assessments will be used as supportive analyses</p><br>
- Secondary Outcome Measures
Name Time Method <p>Overall Survival : compared between the treament arms<br /><br>PFS compared between the treament arms,<br /><br>Overall response rate per treatment arm, compared<br /><br>TTR per treatment arm, compared<br /><br>DCR per treatment arm, compared<br /><br>DOR per treatment arm, compared<br /><br><br /><br>PRO outcomes per treatment arm, compared<br /><br><br /><br>invest safety and tolerability in MEK162+LGX818 and LGX818 treatment arm<br /><br>compare ECOG PS between treatment arms<br /><br><br /><br>characterize the pharmacokinetics of LGX818 and MEK162 </p><br>