Melanoma Clinical Trial

A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors

Summary

This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the MTD(s) and/or RP2D(s) for the dual combination of LGX818 and MEK162 and the triple combination of LGX818 and MEK162 and LEE011, followed each independently by a Phase II part to assess the clinical efficacy and to further assess the safety of the combinations in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous schedule. Oral LEE011 will be administered once daily on a three weeks on, one week off schedule. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. A cycle is defined as 28 days. The dose escalation parts of the trial will be conducted in adult patients with BRAF V600-dependent advanced solid tumors and is expected to enroll at least 18 patients for the dual combination and at least 12 patients for the triple combination. The dose escalation will be guided by a Bayesian logistic regression model (BLRM). Following MTD/RP2D declaration, patients will be enrolled in three Phase II arms for the dual combination and one Phase II arm for the triple combination. All patients will be followed for 30 days for safety assessments after study drugs discontinuation. All patients enrolled in the Phase II part of the study will be followed for survival.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available

Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation
Evidence of measurable disease as determined by RECIST v1.1
World Health Organization (WHO) Performance Status ≤ 2
Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential

Exclusion Criteria:

Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors

Symptomatic or untreated leptomeningeal disease
Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs
Known acute or chronic pancreatitis
History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy
Clinically significant cardiac disease
Patients with abnormal laboratory values at Screening/baseline
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818/MEK162
Previous or concurrent malignancy
Pregnant or nursing (lactating) women
For addition of LEE011 in the triple combination, congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3, brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT >1.5 x ULN.

Other protocol-defined inclusion/exclusion criteria may apply

Study is for people with:

Melanoma

Phase:

Phase 1

Estimated Enrollment:

189

Study ID:

NCT01543698

Recruitment Status:

Active, not recruiting

Sponsor:

Pfizer

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There are 18 Locations for this study

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H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa Florida, 33612, United States
Moffitt McKinley Outpatient Center
Tampa Florida, 33612, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore Maryland, 21287, United States
Massachusetts General Hospital
Boston Massachusetts, 02114, United States
Ophthalmic Consultants of Boston Inc (OCB)
Boston Massachusetts, 02114, United States
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
Chris O'Brien Lifehouse Hospital
Camperdown New South Wales, 02050, Australia
Melanoma Institute Australia
North Sydney New South Wales, 2060, Australia
Westmead Hospital
Westmead New South Wales, 2145, Australia
UZ Leuven Campus Gasthuisberg
Leuven Vlaams Brabant, 3000, Belgium
Sir Mortimer B. Davis-Jewish General Hospital
Montreal Quebec, H3T 1, Canada
Hôpital Saint louis
Paris , 75010, France
Service de radiologie - Hopital Saint Louis
Paris , 75475, France
IRCCS Fondazione Pascale
Naples Campania, 80131, Italy
Azienda Ospedaliera Monaldi
Napoli Campania, 80131, Italy
Azienda Ospedaliera Universitaria Federico II
Napoli Campania, 80131, Italy
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
Milan , 20162, Italy
Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
Napoli , 80131, Italy
National Cancer Centre Singapore
Singapore , 16961, Singapore
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona , 08035, Spain
Hospital Universitario HM Sanchinarro ? CIOCC
Madrid , 28050, Spain
University Hospital Zürich, Dermatology
Zurich-Airport Zurich, 8058, Switzerland
Kantonsspital St. Gallen
St.Gallen , 9007, Switzerland

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 1

Estimated Enrollment:

189

Study ID:

NCT01543698

Recruitment Status:

Active, not recruiting

Sponsor:


Pfizer

How clear is this clinincal trial information?

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