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

NCT ID: NCT01436656

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-05
• Study Completion Date: 2022-11-07

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LGX818 - Dose escalation

Group Type: EXPERIMENTAL

LGX818

Intervention Type: DRUG

LGX818 - Dose Expansion at MTD or RP2D

Group Type: EXPERIMENTAL

LGX818

Intervention Type: DRUG

Interventions

LGX818

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

For the dose escalation phase:

1. 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.

2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.

3. Evidence of measurable disease

Exclusion Criteria

1. Previous therapy with a MEK inhibitor.

2. Symptomatic or untreated leptomeningeal disease.

3. 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.

4. Known acute or chronic pancreatitis.

5. Clinically significant cardiac disease

6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818

8. 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).

9. History of thromboembolic or cerebrovascular events within the last 6 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Western Sydney Local Health District

Westmead, New South Wales, Australia

Westmead Hospital- Redbank Rd

Westmead, New South Wales, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

EDOG - Institut Claudius Regaud - PPDS

Toulouse, Haute-garonne, France

Institut Gustave Roussy

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

Institut Gustave Roussy

Villejuif, VAL DE Marne, France

Institut Gustave Roussy

Villejuif, Val-de-marne, France

Institut Gustave Roussy

Villejuif, , France

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Oslo Myeloma Center - PPDS

Oslo, , Norway

Hospital Clinic de Barcelona

Badalona, , Spain

Hospital General Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , Spain

Hospital Universitario HM Sanchinarro_CIOCC

Madrid, , Spain

START MADRID_Hospital Universitario HM Sanchinarro - CIOCC

Madrid, , Spain

Kantonsspital Graubünden

Chur, Graubünden (DE), Switzerland

Universität Zürich

Zurich, , Switzerland

Countries

United States; Australia; France; Japan; Norway; Spain; Switzerland

Other Identifiers

C4221010

Identifier Type: OTHER

Identifier Source: secondary_id

2011-000556-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLGX818X2101

Identifier Type: -

Identifier Source: org_study_id