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All Drugs and Chemicals

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Radiation therapy

The starting dose of vemurafenib will be the patient's baseline tolerating dose, between 720 - and 960 mg PO bid.

Kenneth Grossmann, MD, PhD

Patients are being asked to take part because they have melanoma that has spread to other organs in their body (metastatic). As part of this study, patients will receive radiation therapy and an approved drug (Vemurafenib).

Patients will be treated with vemurafenib plus radiation therapy (RT) based upon the administration schedule. The starting dose of vemurafenib will be the patient's baseline tolerating dose, between 720 - and 960 mg by mouth. Patients must be tolerating at a minimum 720mg for one cycle (28 days) prior to enrollment.

Radiation Use During Vemurafenib Treatment

Radiation Use During Vemurafenib and Cobimetinib Treatment in Patients With BRAFV600 Mutated Stage IV or Unresectable Stage III Melanoma

To evaluate the safety of radiation combined with vemurafenib treatment in patients with BRAFV600 mutated Stage IV or unresectable Stage III melanoma

To evaluate response rates as assessed by RECIST criteria 1.1, at baseline, and at 8 week intervals throughout the study

University of Utah

LGX818 capsules will be administered orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed 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. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.

LGX818

Paul Chapman, MD

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

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

Overall survival will be calculated for the start of treatment to the date of last death or follow-up.

PK parameters will be determined on PK profiles after the first dose and at steady-state using non-compartmental method(s) using WinNonlin

Efficacy for all patients will be evaluated by the study sites using RECIST v1.1 and response criteria based on contrast-enhanced CT. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Response rate (defined as complete + partial response) and 95% confidence interval will be estimated.

Array BioPharma

Memorial Sloan Kettering Cancer Center

Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation will receive LGX818 capsules orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed 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. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

The protocol was stopped after 7 participants were accrued due to intolerable toxicities.

Dr. Paul Chapman MD

Number of Participants With Response According to RECIST v1.1 Criteria

LGX818 capsules will be administered orally on a once -daily schedule (QD) dosing at a dose of 300 mg/day, 2 weeks on followed 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. After the follow up visit patients will be contacted approximately every 12 weeks until they have received a subsequent therapy or until they have been off treatment for a year to monitor their survival.

LGX818

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiation Use During Vemurafenib Treatment	NCT01843738	BRAFV600 Mutati... Stage IV Melano...	Radiation thera... Vemurafenib	18 Years -	University of Utah
Radiation Use During Vemurafenib Treatment	NCT01843738	BRAFV600 Mutati... Stage IV Melano...	Radiation thera... Vemurafenib	18 Years -	University of Utah
BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation	NCT01894672	Melanoma	LGX818	18 Years -	Memorial Sloan Kettering Cancer Center
BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation	NCT01894672	Melanoma	LGX818	18 Years -	Memorial Sloan Kettering Cancer Center
BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation	NCT01894672	Melanoma	LGX818	18 Years -	Memorial Sloan Kettering Cancer Center
BRAF Inhibitor, LGX818, Utilizing a Pulsatile Schedule in Patients With Stage IV or Unresectable Stage III Melanoma Characterized by a BRAFV600 Mutation	NCT01894672	Melanoma	LGX818	18 Years -	Memorial Sloan Kettering Cancer Center
Radiation Use During Vemurafenib Treatment	NCT01843738	BRAFV600 Mutati... Stage IV Melano...	Radiation thera... Vemurafenib	18 Years -	University of Utah

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