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

• ClinicalTrials.gov Identifier: NCT01436656
• Recruitment Status: Active, not recruiting
• First Posted: September 20, 2011
• Last Update Posted: December 6, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Melanoma and Metastatic Colorectal Cancer	Drug: LGX818	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma
• Actual Study Start Date: September 5, 2011
• Actual Primary Completion Date: October 1, 2012
• Estimated Study Completion Date: July 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: LGX818 - Dose escalation	Drug: LGX818
Experimental: LGX818 - Dose Expansion at MTD or RP2D	Drug: LGX818

Outcome Measures

Primary Outcome Measures :

1. Incidence of Dose Limiting Toxicities [ Time Frame: Approximately every 8 weeks (up to 2 years) ]

Secondary Outcome Measures :

1. Number and nature of Adverse events and clinical activity [ Time Frame: Approximately 3 years ]
2. Pharmacokinetic profile of LGX818 [ Time Frame: Approximately 2 years ]
   LGX818 Plasma concentration
3. Tumor response per RECIST [ Time Frame: Approximately 3 years ]
   This includes duration of response, time to response, progression free survival and overall survival.
4. Baseline molecular status [ Time Frame: Approximately 3 years ]
   Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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
7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

France

EDOG - Institut Claudius Regaud - PPDS

Toulouse, Haute-garonne, France, 31059 Cedex 9

Institut Gustave Roussy

Villejuif, Val-de-marne, France, 94805

Institut Gustave Roussy

Villejuif, France, 94805

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan, 104-0045

Spain

Hospital Clinic de Barcelona

Badalona, Spain, 08036

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, Spain, 08035

Hospital Universitario HM Sanchinarro_CIOCC

Madrid, Spain, 28050

Switzerland

Kantonsspital Graubünden

Chur, Graubünden (DE), Switzerland, 07000

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01436656
• Other Study ID Numbers: CLGX818X2101; C4221010 ( Other Identifier: Alias Study Number ); 2011-000556-42 ( EudraCT Number )
• First Posted: September 20, 2011
• Last Update Posted: December 6, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

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

Additional relevant MeSH terms:

Melanoma; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas