A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

NCT01436656 | Completed Phase 1 Results

• 3 other identifiers: CLGX818X2101C42210102011-000556-42
• Study Type: interventional
• Target: 107
• Locations: 7 countries
• Sites: 24

Brief Summary

CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.

Conditions

Melanoma and Metastatic Colorectal Cancer

Keywords

BRAF mutant,; BRAF mutated,; melanoma,; metastatic,; advanced,; RAF kinase inhibitor; BRAF V600 mutation

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase

  DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: \>=grade (G)3 neutropenia or thrombocytopenia for \>7 days; G4 thrombocytopenia; febrile neutropenia; \>=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (\>=G3 for \> 7 consecutive days or G4); \>=G3 ALT or AST and \>=G2 blood bilirubin; \>=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for \>7 consecutive days; \>= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; \>=G3 pancreatitis, rash/photosensitivity (G3 for \> 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.

  Up to 28 days

• Number of Participants With DLT During Dose Expansion Phase

  DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: \>=grade (G)3 neutropenia or thrombocytopenia for \>7 days; G4 thrombocytopenia; febrile neutropenia; \>=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (\>=G3 for \> 7 consecutive days or G4); \>=G3 ALT or AST and \>=G2 blood bilirubin; \>=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for \>7 consecutive days; \>= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; \>=G3 pancreatitis, rash/photosensitivity (G3 for \> 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.

  Up to 28 days

Secondary Outcomes (26)

• Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Dose Escalation Phase

  From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)

• Number of Participants With AEs and SAEs During Dose Expansion Phase

  From start of study treatment until 30 days after last dose of study treatment (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

• Progression Free Survival (PFS): Dose Escalation Phase

  From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)

• PFS: Dose Expansion Phase

  From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

• Duration of Response (DOR): Dose Escalation Phase

  From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)

Study Arms (2)

LGX818 - Dose escalation

EXPERIMENTAL

Drug: LGX818

LGX818 - Dose Expansion at MTD or RP2D

EXPERIMENTAL

Drug: LGX818

Interventions

LGX818 DRUG

LGX818 - Dose Expansion at MTD or RP2D; LGX818 - Dose escalation

Eligibility Criteria

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

You may qualify if:

• For the dose escalation phase:
• Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
• Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
• Evidence of measurable disease

You may not qualify if:

• Previous therapy with a MEK inhibitor.
• Symptomatic or untreated leptomeningeal disease.
• Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
• Known acute or chronic pancreatitis.
• Clinically significant cardiac disease
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
• 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).
• History of thromboembolic or cerebrovascular events within the last 6 months

Sponsors & Collaborators

• Pfizer: lead

Study Sites (24)

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Western Sydney Local Health District

Westmead, New South Wales, 2145, Australia

Location

Westmead Hospital- Redbank Rd

Westmead, New South Wales, 2145, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

EDOG - Institut Claudius Regaud - PPDS

Toulouse, Haute-garonne, 31059 Cedex 9, France

Location

Institut Gustave Roussy

Villejuif, ILE de France - VAL de Marne (94), 94800, France

Location

Institut Gustave Roussy

Villejuif, VAL DE Marne, 94800, France

Location

Institut Gustave Roussy

Villejuif, Val-de-marne, 94805, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Oslo Myeloma Center - PPDS

Oslo, 00424, Norway

Location

Hospital Clinic de Barcelona

Badalona, 08036, Spain

Location

Hospital General Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 08035, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 8035, Spain

Location

Hospital Universitario HM Sanchinarro_CIOCC

Madrid, 28050, Spain

Location

START MADRID_Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050, Spain

Location

Kantonsspital Graubünden

Chur, Graubünden (DE), 07000, Switzerland

Location

Universität Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Melanoma; Colorectal Neoplasms; Neoplasm Metastasis

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; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2011
• First Posted: September 20, 2011
• Study Start: September 5, 2011
• Primary Completion: October 1, 2012
• Study Completion: November 7, 2022
• Last Updated: October 28, 2024
• Results First Posted: October 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); ES (7); CH (2); FR (5); AU (3); JP (1); US (5)