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
  Purpose

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


Condition Intervention Phase
Melanoma
Drug: LGX818
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 26
Study Start Date: July 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: LGX818

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01894672

Contacts
Contact: Paul Chapman, MD 646-888-4162
Contact: Michael Postow, MD 646-888-4589

Locations
United States, New Jersey
Memorial Sloan-Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States
Contact: Paul Chapman, MD    646-888-4162      
United States, New York
Memorial Sloan-Kettering Cancer Center at Commack Recruiting
Commack, New York, United States, 11725
Contact: Paul Chapman, MD    646-888-4162      
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Paul Chapman, MD    646-888-4162      
Contact: Michael Postow, MD    646-888-4589      
Principal Investigator: Paul Chapman, MD         
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Paul Chapman, MD    646-888-4162      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Paul Chapman, MD    646-888-4162      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Novartis
Investigators
Principal Investigator: Paul Chapman, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01894672     History of Changes
Other Study ID Numbers: 13-053
Study First Received: July 3, 2013
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
LGX818
BRAF Inhibitor
Stage IV melanoma
unresectable stage III melanoma
BRAFV600 mutation
13-053

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 23, 2014