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

Sponsor

Pfizer (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT01436656

Collaborator

(none)

Enrollment

Locations

Arms

130.8

Anticipated Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Sep 5, 2011

Actual Primary Completion Date :

Oct 1, 2012

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: LGX818 - Dose escalation

Drug: LGX818

Experimental: LGX818 - Dose Expansion at MTD or RP2D

Drug: LGX818

Outcome Measures

Primary Outcome Measures

Incidence of Dose Limiting Toxicities [Approximately every 8 weeks (up to 2 years)]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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
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.
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

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	EDOG - Institut Claudius Regaud - PPDS	Toulouse	Haute-garonne	France	31059 Cedex 9
2	Institut Gustave Roussy	Villejuif	Val-de-marne	France	94805
3	Institut Gustave Roussy	Villejuif		France	94805
4	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
5	Hospital Clinic de Barcelona	Badalona		Spain	08036
6	Hospital Universitario Vall d'Hebron - PPDS	Barcelona		Spain	08035
7	Hospital Universitario HM Sanchinarro_CIOCC	Madrid		Spain	28050
8	Kantonsspital Graubünden	Chur	Graubünden (DE)	Switzerland	07000