Trial record 1 of 1 for:    NCT01909453
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Study Comparing Combination of LGX818 Plus MEK162 and LGX818 Monotherapy Versus Vemurafenib in BRAF Mutant Melanoma (COLUMBUS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01909453
First received: July 24, 2013
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

A prospective, randomized, open label, multi-center, parallel group, 3-arm phase III study comparing the efficacy and safety of both, LGX818 plus MEK162 and LGX818 monotherapy, as compared to vemurafenib in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation.

A total of approximately 900 patients will be randomized 1:1:1 to one of 3 treatment arms: 1) LGX818 plus MEK162 (denoted as Combination arm), 2) LGX818 monotherapy (denoted as LGX818 arm), 3) vemurafenib.


Condition Intervention Phase
Melanoma
Drug: LGX818
Drug: LGX818+MEK162
Drug: vemurafenib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized, 3-arm, Open Label, Multicenter Study of LGX818 Plus MEK162 and LGX818 Monotherapy Compared With Vemurafenib in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined based on tumor assessment (RECIST version 1.1 criteria) as per Blinded Independent Review Committee (BIRC) and survival information. The local Investigator's assessments will be used as supportive analyses.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Up to approximately 4 years after first patient randomized ] [ Designated as safety issue: No ]
    OS is calculated as the time from date of randomization to date of death due to any cause.

  • Progression Free Survival (PFS) [ Time Frame: Approximately 2 years with update around 3 years after first patient randomized ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined based on tumor assessment (RECIST version 1.1 criteria) as per Blinded Independent Review Committee (BIRC) and survival information. The local Investigator's assessments will be used as supportive analyses.

  • Objective Response Rate (ORR) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    ORR calculated as the proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and unconfirmed responses separately.

  • Time To Response (TTR) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    TTR calculated as the time from date of randomization until first documented complete response (CR) or partial response(PR).

  • Disease Control Rate (DCR) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    DCR calculated as the proportion of patient with a best overall response of CR, PR or stable disease (SD)

  • Duration of objective response (DOR) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer

  • Safety and tolerability of combination and LGX818 [ Time Frame: Up to approximately 4 years after first patient randomized ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events and serious adverse events , changes in laboratory values, vital signs, electrocardiograms (ECGs), MUGA (Multi-Gated Acquisition Scan)/echocardiogram and assessment of physical, dermatological and ocular examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  • ECOG Performance status (PS) [ Time Frame: Approximatley 2 years after first patient randomized ] [ Designated as safety issue: No ]
    Change from baseline in the ECOG PS

  • Time to definitive 1 point deterioration in ECOG performance status [ Time Frame: Approximatley 2 years after first patient randomized ] [ Designated as safety issue: No ]
    Time to definitive 1 point deterioration in the ECOG PS is defined as the time form date of randomization to definitive deterioration, where deterioration is considered as definitive if no improvement in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.

  • Pharmacokinetics of LGX818 and MEK162 [ Time Frame: Approximatley 2 years after first pateint randomized ] [ Designated as safety issue: No ]
    Plasma concentration-profiles of LGX818 and MEK162 and model based PK parameters

  • Time to definitive 10% deterioration in global health status (EORTC QLQC30) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    Time to definitive 10% deterioration in the global health status score of the EORTC QLQ-C30 is the time from the date of randomization to the date of at least 10% relative to baseline worsening with no later improvement above this threshold observed during the course of the study or death due to any cause

  • Global health status (EORTC QLQC30) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    Change from baseline in the global health status score of the EORTC QLQ-C30

  • Time to definitive 10% deterioration in the FACT-M melanoma subscale [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    Time to definitive 10% deterioration in the FACT-M melanoma (subscale) is the time from the date of randomization to the date of at least 10% relative to baseline worsening with no later improvement above this threshold observed during the course of the study or death due to any cause

  • Global health status (EQ-5D) [ Time Frame: Approximately 2 years after first patient randomized ] [ Designated as safety issue: No ]
    Change from baseline in the EQ-5D


Estimated Enrollment: 900
Study Start Date: September 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LGX818
LGX818 300 mg QD
Drug: LGX818
LGX818- Orally 300 mg once daily (3 X 100 mg capsules) with a glass of water. Patients should be fasted 2 hours before and 1 hour after the dose. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent.
Experimental: LGX818+MEK162
LGX818 450 mg QD + MEK162 45mg BID
Drug: LGX818+MEK162
LGX818- Orally 450 mg once daily (4 X 100 mg capsules + 1 X 50 mg capsule) with a glass of water. Patients should be fasted 2 hours before and 1 hour after the dose. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent. MEK162- Orally 45 mg twice daily (3 X 15 mg tablets) Medication should be taken with a glass of water. Patients should be fasted 2 hours before and 1 hour after the dose. Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent.
Active Comparator: vemurafenib
vemurafenib 960 mg BID
Drug: vemurafenib
960 mg twice daily (4 X 240 mg tablets). Treatment will be administered until disease progression, unacceptable toxicity or withdrawal of consent.
Other Names:
  • Zelboraf
  • PLX4032
  • RO5185426

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma (AJCC Stage IIIB, IIIC, or IV)
  • Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization
  • Naïve untreated patients or patients who have progressed on or after prior first line immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy or radiotherapy), except the administration of BRAF or MEK inhibitors
  • Evidence of at least one measurable lesion as detected by radiological or photographic methods
  • ECOG performance status of 0 or 1
  • Adequate bone marrow, organ function, cardiac and laboratory parameters
  • Normal functioning of daily living activities

Exclusion Criteria:

  • Any active/non-stable brain lesion
  • Non-cutaneous melanoma
  • History of leptomeningeal metastases
  • History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease.
  • Any previous chemotherapy treatment, extensive radiotherapy or investigational agent other than immunotherapy, or patients who have received more than one line of immunotherapy for locally advanced unresectable or metastatic melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at least 6 weeks prior to randomization
  • History of Gilbert's syndrome
  • Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor
  • Impaired cardiovascular function or clinically significant cardiovascular diseases
  • Uncontrolled arterial hypertension despite medical treatment
  • HIV positive or active Hepatitis B, and/or active Hepatitis C
  • Impairment of gastrointestinal function
  • Patients with neuromuscular disorders that are associated with elevated CK.
  • Pregnant or nursing (lactating) women
  • Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
  • Other protocol-defined inclusion/exclusion criteria may apply
  • Patients taking non-topical medication known to be a strong inhibitor of CYP3A4. However patients who either discontinue their treatment or switch to another medication at least three days prior to randomization are eligible

Other protocol-defined inclusion/exclusion criteria may apply. NVS Definition: List only the main study specific inclusion/exclusion criteria that patients will understand.

Note: DO NOT cut/paste directly from the protocol.

Do not include age and gender as part of this field. Age and gender are indicated in the 2 fields below.

Always include statement "Other protocol-defined inclusion/exclusion criteria may apply" at the end of this section.

Examples:

Inclusion criteria:

Patients within 7- 42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction Qualifying Echocardiogram at Visit 1

Exclusion criteria:

Presence of clinically overt heart failure Percutaneous coronary intervention (PCI) less than 24 hours before randomization previous treatment with aliskiren

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01909453

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 277 Study Locations
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: NCT01909453     History of Changes
Other Study ID Numbers: CMEK162B2301
Study First Received: July 24, 2013
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration
Australia: National Health and Medical Research Council
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: The Italian Medicines Agency
Argentina: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Hungary: Institutional Ethics Committee
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Turkey: Ministry of Health
Brazil: Ministry of Health

Keywords provided by Novartis:
Melanoma
Cutaneous melanoma
Skin disease
Skin cancer
Skin Neoplasms
Neoplasm Metastasis
BRAF mutant
BRAF V600E
BRAF V600K
cancer
LGX818
MEK162
vemurafenib
combination
BRAF inhibitor
MEK inhibitor
Phase III

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 16, 2014