LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma

NCT01820364 | Terminated Phase 2 Results

• 2 other identifiers: CLGX818X21022012-004798-17
• Study Type: interventional
• Target: 15
• Locations: 6 countries
• Sites: 6

Brief Summary

The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents.

Conditions

Melanoma

Keywords

open-label study; BRAF inhibitor; LGX818; MEK1620; MAPK1/2 inhibitor; Pi3K inhibitor; FGFR; c-Met; CDK4/6; metastatic melanoma; BRAF; V600

Outcome Measures

Primary Outcomes (1)

• Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II)

  Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define the status of tumors in cancer patients during a specific treatment. The Overall Response Rate was calculated according to the RECIST criteria, as per investigator assessment. Per RECIST guidelines: * Complete Response (CR) is the Disappearance of all target lesions. * Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions. * Progressive Disease (PD) is the at least a 20% increase in the sum of diameters of target lesions. * Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  Baseline through study completion (approximately 2 years)

Secondary Outcomes (5)

• Incidence of Dose Limiting Toxicities (DLTs) (Part II)

  Baseline through study completion (approximately 2 years)

• Plasma Concentration and Derived Pharmacokinetic Parameters

  Baseline through study completion (approximately 2 years)

• Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I)

  Baseline through completion of Part I of the study (approximately 2 years)

• Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II)

  Entry to Part II of the study through study completion (approximately 22 days)

• Molecular Status of Markers Relevant to the RAP/MEK/ERK and PI3K/AKT Pathways

  Baseline and at progression with LGX818 single agent treatment

Study Arms (1)

LGX818 single agent

EXPERIMENTAL

Patients had to have written documentation of a BRAFV600 mutation, which was to have been obtained locally on a fresh tumor biopsy (preferred) or on the most recent archival tumor sample available.

Drug: LGX818

Interventions

LGX818 DRUG

BRAF inhibitor. LGX818 was administered QD orally on a daily schedule (21-day cycles) as a flat-fixed dose and not by body weight or body surface area. LGX818 100 mg capsules and 50 mg capsules.

Also known as: encorafenib

LGX818 single agent

Eligibility Criteria

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

You may qualify if:

• locally advanced or metastatic melanoma
• confirmed BRAF V600 mutation
• patients naïve to a selective BRAF inhibitor
• fresh tumor biopsy at baseline, and patient agrees for a mandatory biopsy at the time of relapse
• life expectancy ≥ 3 months
• World Health Organization (WHO) Performance Status ≤ 2.

You may not qualify if:

• Previous treatment with RAF-inhibitor
• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastases.
• Known acute or chronic pancreatitis
• Clinically significant cardiac disease
• AST/SGOT and ALT/SGPT \> 2.5 x ULN, or \> 5 x ULN if liver metastases are present
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral interventional drug
• Previous or concurrent malignancy.
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation
• LGX818/MEK162:
• History or current evidence of retinal disease History of Gilbert's syndrome.
• LGX818/BKM120:
• Patients with diabetes mellitus requiring insulin treatment Patient has mood disorders
• LGX818/BGJ398:
• History and/or current evidence of ectopic mineralization/ calcification Current evidence of corneal disorder/ keratopathy Patients with current evidence of endocrine alteration of calcium/phosphate homeostasis.

Sponsors & Collaborators

• Array BioPharma: lead

Study Sites (6)

Sarah Cannon Research Institute Onc Dept

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

East Melbourne, Victoria, 3002, Australia

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

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

Recruitment halted on 26-Jul-2014, which led to small numbers of subjects analyzed. This recruitment halt was not a consequence of any safety concern and patients who were ongoing in the study continued to be treated as per protocol.

Results Point of Contact

• Title: Study Director
• Organization: Array BioPharma, Inc.

clinicaltrials@arraybiopharma.com

303-381-6604

Study Officials

• Array BioPharma

  303-381-6604

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: March 28, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: January 9, 2017
• Results First Posted: January 9, 2017

Record last verified: 2016-11

Locations

CH (1); CA (1); DE (1); US (1); AU (1); ES (1)