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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01909453
Recruitment Status : Active, not recruiting
First Posted : July 26, 2013
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 24, 2013
First Posted Date  ICMJE July 26, 2013
Last Update Posted Date November 16, 2020
Actual Study Start Date  ICMJE September 16, 2013
Actual Primary Completion Date November 9, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2013)
Progression free survival (PFS) [ Time Frame: Approximately 2 years after first patient randomized ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2016)
  • Overall Survival (OS) [ Time Frame: Up to approximately 5 years after first patient randomized ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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: Approximately 2 years after first patient randomized ]
    Change from baseline in the ECOG PS.
  • Time to definitive 1 point deterioration in ECOG performance status [ Time Frame: Approximately 2 years after first patient randomized ]
    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: Approximately 2 years after first patient randomized ]
    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 ]
    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 ]
    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 ]
    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 ]
    Change from baseline in the EQ-5D.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2013)
  • Overall Survival (OS) [ Time Frame: Up to approximately 4 years after first patient randomized ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Time to definitive 1 point deterioration in the ECOG PS is defined as the time form date of randomization to definitive deterioration, where deteriorationis 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 ]
    Plasma concentration-profiles of LGX818 and MEK162 and model based PK parameters
  • Time to definitive 10% deteriortaion in global health status (EORTC QLQC30) [ Time Frame: Approximately 2 years after first patient randomized ]
    Time to definitive 10% deterioration in the global health status score of theEORTC 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 ]
    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 ]
    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 ]
    Change from baseline in the EQ-5D
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
Official Title  ICMJE A 2-part Phase III Randomized, Open Label, Multicenter sSudy of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Brief Summary

This is 2-part, randomized, open label, multi-center, parallel group, phase III study comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818 monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. A total of approximately 900 patients will be randomized.

Part 1:

Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms:

  1. LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm)
  2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or
  3. vemurafenib 960 mg BID (denoted as vemurafenib arm)

Part 2:

Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms:

  1. LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or
  2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: LGX818
    LGX818- Orally 100 mg and 50 mg capsules
  • Drug: MEK162
    MEK162- Orally 15 mg tablets
  • Drug: vemurafenib
    Tablets in bottles or blisters 240 mg
    Other Names:
    • Zelboraf
    • PLX4032
    • RO5185426
Study Arms  ICMJE
  • Experimental: LGX818 450 mg + MEK162
    LGX818 450 mg QD + MEK162 45 mg BID
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
  • Active Comparator: Vemurafenib
    Vemurafenib 960 mg BID
    Intervention: Drug: vemurafenib
  • Experimental: LGX818 300 mg + MEK162
    LGX818 300 mg QD + MEK162 45 mg BID
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
  • Experimental: LGX818
    LGX818 300 mg QD
    Intervention: Drug: LGX818
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 3, 2016)
921
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2013)
900
Estimated Study Completion Date  ICMJE August 31, 2022
Actual Primary Completion Date November 9, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary 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, radiotherapy or chemotherapy), 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 untreated central nervous system (CNS) lesion
  • Uveal and mucosal 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 systemic 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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   Colombia,   Czechia,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01909453
Other Study ID Numbers  ICMJE CMEK162B2301
C4221004 ( Other Identifier: Pfizer )
2013-001176-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP