A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
This study is currently recruiting participants.
Verified September 2012 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01543698
First received: February 1, 2012
Last updated: September 28, 2012
Last verified: September 2012
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Purpose
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 combination of LGX818 and MEK162, followed by a Phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous 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 part 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. 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. 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Solid Tumors Harboring a BRAF V600 Mutation |
Drug: LGX818 Drug: MEK162 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label |
| Official Title: | A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors |
Resource links provided by NLM:
Genetics Home Reference related topics:
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MedlinePlus related topics:
Cancer
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- Phase Ib: Estimation of Maximum Tolerated Dose (MTD) by measuring incidence of dose limiting toxicities (DLT) [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]To estimate the MTD(s) and/or rapid phase 2 dose(s) (RP2D(s)) of oral LGX818 in combination with oral MEK162 in patients with BRAF V600-dependent advanced solid tumors by measuring the incidence of DLTs as defined by the protocol.
- Phase II: Clinical efficacy [ Time Frame: up to 14 months ] [ Designated as safety issue: Yes ]Assess clinical efficacy of the LGX818 and MEK162 combination by evaluating the disease control rate (DCR) and objective response rate (ORR) as per RECIST 1.1
Secondary Outcome Measures:
- Safety and tolerability of LGX818 and MEK162 by evaluating the incidence and severity of adverse events (AE). [ Time Frame: up to 17 months ] [ Designated as safety issue: Yes ]To characterize the safety and tolerability of LGX818 and MEK162 in combination by evaluating the incidence and severity (as per CTCAE grading) of AEs in all patients enrolled in the study.
- Determination of single and multiple dose of Pharmacokinetics (PK) profile by measuring plasma concentrations versus time after study drug combination dosing (Phase Ib) [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]To determine the single and multiple dose PK profile of the LGX818 and MEK162 combination by measuring plasma concentrations of MEK162 and LGX818 resp. at different timepoints prior and post study drug combination dosing on several days within cycle 1 and subsequent cycles.
- Preliminary clinical anti-tumor activity by evaluating the objective response rate (Phase Ib) [ Time Frame: up to 8 months ] [ Designated as safety issue: No ]
To assess preliminary anti-tumor activity of the LGX818 and MEK162 combination by evaluating the ORR as per RECIST 1.1.
Safety Issue?: (FDAAA) No
- Further clinical efficacy (phase II) [ Time Frame: up to 14 months ] [ Designated as safety issue: No ]To further assess clinical efficacy of the LGX818 and MEK162 combination in the Phase II populations by measuring progression free survival (PFS) as per RECIST 1.1
| Estimated Enrollment: | 127 |
| Study Start Date: | May 2012 |
| Estimated Study Completion Date: | March 2015 |
| Estimated Primary Completion Date: | March 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: LGX818 QD and MEK162 BID
combination
|
Drug: LGX818 Drug: MEK162 |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01543698
Contacts
| Contact: Novartis Pharmaceuticals | +1(800)340-6843 |
Locations
| United States, Florida | |
| H. Lee Moffitt Cancer Center/University of South Florida Moffitt SC 2 | Not yet recruiting |
| Tampa, Florida, United States, 33612 | |
| Contact: Amber Isley 813-745-4798 amber.isley@moffitt.org | |
| Principal Investigator: Ragini Kudchadkar | |
| United States, Maryland | |
| The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins | Not yet recruiting |
| Baltimore, Maryland, United States, 21231 | |
| Contact: Melinda Downs 410-502-2377 mhalter1@jhmi.edu | |
| Principal Investigator: David Cosgrove | |
| United States, Massachusetts | |
| Massachusetts General Hospital Mass General 2 | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Rosemary Boyle 617-724-0865 rboyle1@partners.org | |
| Principal Investigator: Keith Flaherty | |
| United States, Texas | |
| MD Anderson Cancer Center/University of Texas MD Univ TX | Not yet recruiting |
| Houston, Texas, United States, 77030-4009 | |
| Contact: Investigational Drug 713-792-8874 invdrugs@mdanderson.org | |
| Principal Investigator: Kevin B Kim | |
| Australia, New South Wales | |
| Novartis Investigative Site | Not yet recruiting |
| Camperdown, New South Wales, Australia, 2050 | |
| Novartis Investigative Site | Recruiting |
| Westmead, New South Wales, Australia, 2145 | |
| Canada, Quebec | |
| Novartis Investigative Site | Recruiting |
| Montreal, Quebec, Canada, H3T 1E3 | |
| France | |
| Novartis Investigative Site | Not yet recruiting |
| Paris, France, 75475 | |
| Singapore | |
| Novartis Investigative Site | Recruiting |
| Singapore, Singapore, 169610 | |
| Spain | |
| Novartis Investigative Site | Recruiting |
| Barcelona, Cataluña, Spain, 08035 | |
| Novartis Investigative Site | Not yet recruiting |
| Madrid, Spain, 28050 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01543698 History of Changes |
| Other Study ID Numbers: | CMEK162X2110, 2011-005875-17 |
| Study First Received: | February 1, 2012 |
| Last Updated: | September 28, 2012 |
| Health Authority: | United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Canada: Health Canada Singapore: Health Sciences Authority Spain: Agencia Espaniola de Medicamentos y Productos Sanitarios Switzerland: Swiss Agency for Therapeutic Products (Swissmedic) Italy:National Institute of Health (Istituto Superiore di Sanita) France: AFSSAPS - Agence française de sécurité sanitaire des produits de santé Belgium: Federal Agency for Medicines and Health Products (FAMHP) |
Keywords provided by Novartis:
|
Advanced solid tumor, BRAF V600 mutation |
Additional relevant MeSH terms:
|
Neoplasms |
ClinicalTrials.gov processed this record on October 17, 2012
