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History of Changes for Study: NCT02159066
LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma (LOGIC-2)
Latest version (submitted June 11, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 5, 2014 None (earliest Version on record)
2 June 17, 2014 Contacts/Locations, Eligibility and Study Status
3 June 18, 2014 Study Status and Contacts/Locations
4 September 5, 2014 Recruitment Status, Contacts/Locations, Study Status and Oversight
5 December 1, 2014 Contacts/Locations and Study Status
6 February 7, 2015 Contacts/Locations, Study Status, Eligibility and Study Description
7 March 18, 2015 Contacts/Locations and Study Status
8 October 6, 2015 Contacts/Locations, Study Status and Outcome Measures
9 November 18, 2015 Contacts/Locations, Study Status, Sponsor/Collaborators and Study Identification
10 November 20, 2015 Contacts/Locations and Study Status
11 February 11, 2016 Recruitment Status, Contacts/Locations and Study Status
12 February 13, 2017 Study Status and Oversight
13 February 17, 2017 Study Status
14 March 29, 2017 Study Status
15 December 22, 2017 Study Status and Contacts/Locations
16 January 2, 2019 Study Status
17 February 27, 2019 Study Status
18 March 12, 2020 Study Status
19 June 24, 2020 Contacts/Locations, Study Identification, Sponsor/Collaborators, Study Status and IPDSharing
20 September 1, 2020 Contacts/Locations, Study Status, Study Design and Study Identification
21 November 11, 2020 Contacts/Locations and Study Status
22 February 5, 2021 Contacts/Locations, Study Status, Study Design and Study Identification
23 May 11, 2021 Study Status and Contacts/Locations
24 June 11, 2021 Study Status and Contacts/Locations
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Study NCT02159066
Submitted Date:  June 5, 2014 (v1)

Open or close this module Study Identification
Unique Protocol ID: CLGX818X2109
Brief Title: LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma (LOGIC-2)
Official Title: A Phase II, Multi-center, Open-label Study of Sequential LGX818/MEK162 Combination Followed by a Rational Combination With Targeted Agents After Progression, to Overcome Resistance in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2014
Overall Status: Not yet recruiting
Study Start: June 2014
Primary Completion: January 2017 [Anticipated]
Study Completion: January 2017 [Anticipated]
First Submitted: April 28, 2014
First Submitted that
Met QC Criteria:
June 5, 2014
First Posted: June 9, 2014 [Estimate]
Last Update Submitted that
Met QC Criteria:
June 5, 2014
Last Update Posted: June 9, 2014 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.
Detailed Description:

This study consists of two parts: in Part I, patients naïve to selective BRAF and MEK inhibitors will be treated with the LGX818/MEK162 combination until disease progression (as defined per RECIST v1.1). Based on the genetic analysis of a tumor biopsy obtained at that time, patients will enter Part II of the study for tailored combination treatment in one of four arms of LGX818/MEK162 + either BKM120, BGJ398, INC280 or LEE011 Patients with BRAF mutant melanoma treated by LGX818/MEK162 combination in other studies can be enrolled directly in Part II of CLGX818X2109 after relapse.

Dose-escalations in the combination arms for which no MTD has been established will be based on the recommendations of a Bayesian logistic regression model guided by an escalation with overdose control criterion

Open or close this module Conditions
Conditions: Melanoma
Keywords: Melanoma
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 5
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 140 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: LGX818 + MEK162 Drug: LGX818
Combination of LGX818 and MEK162 (Part I)
Drug: MEK162
Combination of LGX818 and MEK162 (Part I)
Experimental: LGX818 + MEK162 + LEE011 Drug: LEE011
Combination of LGX818 + MEK162 + LEE011 (Part II)
Experimental: LGX818 + MEK162 + BGJ398 Drug: BGJ398
Combination of LGX818 + MEK162 + BGJ398 (Part II)
Experimental: LGX818 + MEK162 + BKM120 Drug: BKM120
Combination of LGX818 + MEK162 + BKM120 (Part II)
Experimental: LGX818 + MEK162 + INC280 Drug: INC280
Combination of LGX818 + MEK162 + INC280 (Part II)
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Overall Response Rate (ORR) (Part II)
[ Time Frame: 2 years ]

Secondary Outcome Measures:
1. Incidence of adverse events
[ Time Frame: 2 years ]

2. Incidence rate of Dose Limiting Toxicities (DLTs)
[ Time Frame: 2 years ]

in Cycle 1 of Combination Part (Part II); cycle 1 = 21 days or 28 days
3. Plasma Pharmacokinetics (PK) parameters of LGX818 + MEK162 and triple combination partners
[ Time Frame: 2 years ]

AUCtau, ss; Cmax; Cmax, ss; Tmax; Tmax, ss; Ctrough; Clast, ss; T1/2, ss; CL,ss/F; Vz,ss/F
4. Overall Response Rate (ORR) (Part II)
[ Time Frame: 2 years ]

5. Progression Free Survival (PFS)(Part I and II)
[ Time Frame: 2 years ]

6. Duration Of Response (DOR) (Part I and II)
[ Time Frame: 2 years ]

7. Overall Survival (OS) (Part II)
[ Time Frame: 2 years ]

8. Molecular status
[ Time Frame: baseline, at progression with LGX818 + MEK162 combination treatment up to 2 years ]

Molecular Status includes mutation, amplification, expression of markers relevant to the RAF/MEK/ERK and PI3K/AKT pathways
9. Time to Response (TTR) (Part I and II)
[ Time Frame: 2 years ]

10. Disease Control Rate (DCR) (Part I and II)
[ Time Frame: 2 years ]

11. Severity of adverse events
[ Time Frame: 2 years ]

Other Outcome Measures:
1. changes in the mutational status in circulating tumor DNA
[ Time Frame: at baseline, on-treatment and at progression up to 2 years. ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

INCLUSION CRITERIA:

  • Age ≥ 18 years at the start of dosing
  • Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer [AJCC])
  • Documented evidence of BRAF V600 mutation.
  • Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated.
  • Evidence of measurable disease, as determined by RECIST v1.1.
  • Life expectancy ≥ 3 months.

INCLUSION CRITERIA for triple combinations:

Progressive disease following prior treatment with LGX818/MEK162 combination. PRINCIPAL EXCLUSION CRITERIA

  • Symptomatic or untreated leptomeningeal disease Symptomatic or untreated leptomeningeal disease.
  • Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for four weeks are allowed to enroll. Brain metastases must be stable at least 4 weeks with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs.
  • Known acute or chronic pancreatitis.
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);
  • Clinically significant cardiac disease including any of the following:
  • CHF requiring treatment (NYH grade ≥ 2),
  • LVEF < 50% as determined by MUGA scan or ECHO
  • History or presence of clinically significant ventricular arrhythmias or atrial fibrillation
  • Clinically significant resting bradycardia
  • Unstable angina pectoris ≤ 3 months prior to starting study drug
  • Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug,
  • QTcF > 480 msec. Patients with any of the following laboratory values at

Screening/baseline:

  • Absolute neutrophil count (ANC) <1,500/mm3 [1.5 x 109/L]
  • Platelets < 100,000/mm3 [100 x 109/L]
  • Hemoglobin < 9.0 g/dL
  • Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% LLN (lower limit of normal)
  • Serum total bilirubin >1.5 x ULN
  • AST/SGOT or ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present

Additional exclusion criteria for the triple combinations:

LGX818/MEK162/BKM120:

  • Patients with fasting glucose > 120 mg/dL or 6.7 mmol/L, and HbA1c > 8 %.
  • Patient has any of the following mood disorders as judged by the

Investigator or a Psychiatrist:

  • Patient has a score ≥ 12 on the PHQ-9 questionnaire
  • Patient has ≥ CTCAE grade 3 anxiety

LGX818/MEK162/BGJ398:

  • History and/or current evidence of significant ectopic mineralization/ calcification with the exception of calcified lymph nodes and asymptomatic vascular calcification.
  • Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivits etc., confirmed by ophthalmologic examination

LGX818/MEK162/LEE011:

  • Patients with uncontrolled hypertension (please refer to WHO-ISHguidelines) are excluded from study.
  • QTcF >450 ms for males and >470 ms for females Congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3 and magnesium levels below the clinically relevant lower limits at study entry
  • Current evidence of brain metastasis or brain metastasis detected by mandatory CT/MRI at screening
  • PT/INR or aPTT > 1.5xULN
Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: 1-888-669-6682
Central Contact Backup: Novartis Pharmaceuticals
Study Officials: Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals
Locations: United States, California
University of California at Los Angeles Onc Dept
Los Angeles, California, United States, 90095
Contact:Contact: Dean Goldstein 310-794-2464 dgoldstein@mednet.ucla.edu
Contact:Principal Investigator: Bartosz Chmielowski
United States, Massachusetts
Massachusetts General Hospital Dept of Onc.
Boston, Massachusetts, United States, 02114
Contact:Contact: Azra Haider 617-632-5470 AHAIDER1@partners.org
Contact:Principal Investigator: Keith T. Flaherty
United States, New York
Memorial Sloan Kettering Cancer Center Dept Oncology
New York, New York, United States, 10021
Contact:Contact: Armando Sanchez 646-888-4339 sanchea2@mskcc.org
Contact:Principal Investigator: Michael Postow
United States, Oregon
Oregon Health & Science University Onc. Dept
Portland, Oregon, United States, 97239
Contact:Contact: Kirsten Orand 503-418-9916 orand@ohsu.edu
Contact:Principal Investigator: Matthew Taylor
United States, Tennessee
Sarah Cannon Research Institute Onc. Dept
Nashville, Tennessee, United States, 37203
Contact:Contact: Heather Pedigo 615-329-7432 Heather.Pedigo@scresearch.net
Contact:Principal Investigator: Jeffrey R. Infante
Vanderbilt University Medical Center Dept. Of Onc.
Nashville, Tennessee, United States, 37232
Contact:Contact: Lindsey Horner 615-936-5867 Lindsey.horner@vanderbilt.edu
Contact:Principal Investigator: Jeffrey A. Sosman
United States, Texas
University of Texas/MD Anderson Cancer Center Dept of Onc.
Houston, Texas, United States, 77030-4009
Contact:Contact: Shelia Lister 713-563-0536 slister@mdanderson.org
Contact:Principal Investigator: Sapna P. Patel
Cancer Therapy & Research Center / UT Health Science Center Dept of Onc
San Antonio, Texas, United States, 78229
Contact:Contact: Lisa Creighton 210-450-1789 Regulatoryaffairs@uthscsa.edu
Contact:Principal Investigator: John Sarantopoulos
United States, Utah
University of Utah / Huntsman Cancer Institute Onc Dept
Salt Lake City, Utah, United States, 84103
Contact:Contact: Rian Davis 801-587-5597 Rian.Davis@hci.utah.edu
Contact:Principal Investigator: Kenneth Grossmann
Australia, Victoria
Novartis Investigative Site
Melbourne, Victoria, Australia, 3002
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3T 1E2
Germany
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Muenchen, Germany, 80336
Novartis Investigative Site
W├╝rzburg, Germany, 97080
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Spain, Catalunya
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Switzerland
Novartis Investigative Site
Zuerich, Switzerland, 8091
United Kingdom
Novartis Investigative Site
Oxford, United Kingdom, OX3 7LJ
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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