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

NCT01894672 | Completed Phase 2 Results

• 1 other identifier: 13-053
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Melanoma

Keywords

LGX818; BRAF Inhibitor; Stage IV melanoma; unresectable stage III melanoma; BRAFV600 mutation; 13-053

Outcome Measures

Primary Outcomes (1)

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

  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.

  1.5 years

Secondary Outcomes (1)

• Response Rate

  1.5 years

Other Outcomes (2)

• Overall Survival

  1.5 years

• Pharmacokinetic (PK) Analysis: Geometric Mean of Maximum Observed Concentration (Cmax) of LGX818 at Steady State

  Cycle 1 - Day 1, 15; Cycle 2 - Day 15; Cycle 3 - Day 1, Day 15

Study Arms (1)

LGX818

EXPERIMENTAL

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.

Drug: LGX818

Interventions

LGX818 DRUG

LGX818

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Array BioPharma: collaborator

Study Sites (5)

Memorial Sloan Kettering Cancer Center at Basking Ridge

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center at Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Melanoma

Interventions

encorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Paul Chapman MD
• Organization: Memorial Sloan Kettering Cancer Center

chapmanp@MSKCC.ORG

646-888-4162

Study Officials

• Paul Chapman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2013
• First Posted: July 10, 2013
• Study Start: July 1, 2013
• Primary Completion: March 17, 2016
• Study Completion: March 17, 2016
• Last Updated: July 16, 2024
• Results First Posted: July 24, 2017

Record last verified: 2019-12

Locations

US (5)