BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01894672
First received: July 3, 2013
Last updated: July 10, 2014
Last verified: July 2014

July 3, 2013
July 10, 2014
July 2013
July 2015   (final data collection date for primary outcome measure)
efficacy [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Efficacy for all patients will be evaluated by the study sites using RECIST v1.1 and response criteria based on contrast-enhanced CT
Same as current
Complete list of historical versions of study NCT01894672 on ClinicalTrials.gov Archive Site
  • overall survival [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    Overall survival will be calculated for the start of treatment to the date of last death or follow-up.
  • response rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    Response rate (defined as complete + partial response) and 95% confidence interval will be estimated.
  • safety [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
    Frequencies of toxicities will be tabulated according to the CTCAE (version 4.03).
  • Pharmacokinetics [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    PK parameters will be determined on PK profiles after the first dose and at steady-state using non-compartmental method(s) using WinNonlin (Pharsight, Mountain View, CA).
Same as current
Not Provided
Not Provided
 
BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation
A Phase 2 Trial of the BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation

The purpose of this phase II study is to find out if an investigational drug called LGX818 can stop the melanoma from growing.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
Drug: LGX818
Experimental: LGX818
LGX818 capsules will be administered orally on a once -daily schedule (QD) dosing for the first 6 weeks. This will be followed by a 2 week break. Thereafter, patients will resume LGX818 on a once daily schedule at a dose of 300 mg/day for 2 weeks followed again by a 2 week break. This schedule of 2 weeks on, followed by 2 weeks off, will continue for the duration of time the patients remains on the clinical trial.
Intervention: Drug: LGX818
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
26
July 2015
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Stage IV, or unresectable stage III melanoma that harbors a BRAFV600 mutation
  • Any prior therapy allowed except a BRAF or MEK inhibitor,.
  • Patients must provide written informed consent prior to any screening procedures.
  • Age 18 years or older.
  • Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Patient is able to swallow and retain oral medication
  • Measurable disease according to RECIST v1.1
  • ECOG performance status ≤ 1

Exclusion Criteria:

  • Brain metastasis or leptomeningeal disease
  • Known acute or chronic pancreatitis
  • Prior colectomy
  • Clinically significant cardiac disease including any of the following:
  • CHF requiring treatment (NYHA Classification ≥ 2) in which patients have a history of LVEF < 45% as determined by MUGA scan or ECHO, or uncontrolled hypertension (please refer to WHO-ISH guidelines)
  • History or presence of clinically significant ventricular arrhythmias or atrial fibrillation
  • Clinically significant resting bradycardia
  • Unstable angina pectoris ≤ 3 months prior to starting study drug
  • Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug
  • QTcF> 480 msec
  • Patients with any of the following laboratory values at Screening/baseline:
  • Absolute neutrophil count (ANC) <1,500/mm3 [1.5 x 109/L]
  • Platelets <100,000/mm3 [100 x 109/L]
  • Hemoglobin < 9.0 g/dL
  • Serum creatinine>1.5 x ULN
  • Serum total bilirubin >1.5 x ULN
  • AST/SGOT and/or ALT/SGPT > 2.5 x ULN
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  • Previous or concurrent malignancy. Exceptions: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  • 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 (> 5 mIU/mL).

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study UNLESS they are using highly effective methods of contraception throughout the study and for 3 months after study drug discontinuation. Highly effective contraception methods include:

Total abstinence or

  • Male or female sterilization
  • Combination of any two of the following (a+b or a+c or b+c)

    1. Use of oral, injected, or implanted hormonal methods of contraception
    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
    3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

      • Post-menopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum Follicle-Stimulating Hormone (FSH) levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Sexually active males must use a condom during intercourse while taking the drug and for 5 T1/2 after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.

  • Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery.
  • Known Human Immunodeficiency Virus (HIV) infection
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
  • Treatment with a prior BRAF or MEK inhibitor
Both
18 Years and older
No
Contact: Paul Chapman, MD 646-888-4162
Contact: Michael Postow, MD 646-888-4589
United States
 
NCT01894672
13-053
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Novartis
Principal Investigator: Paul Chapman, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP