LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma (LOGIC)

November 10, 2016 updated by: Array BioPharma

Phase II, Multi-center, Open-label Study of Single-agent LGX818 Followed by a Rational Combination With Agents After Progression on LGX818, in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma

The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase II two part multi-center, open-label study. Part I: LGX818 single agent treatment until progression Part II: Combination treatments of LGX818 + MEK162, or BKM120, or BGJ398, or INC280, or LEE01 to assess the clinical efficacy, to further evaluate the safety of the drug combinations in patients with locally advanced or metastatic BRAF mutant melanoma after relapse on LGX818, and to determine the maximum tolerated dose of the combinations (when not established previously). These drug combinations are selected and assigned to patients based on documentation of molecular resistance mechanism.

Patients with BRAF mutant melanoma treated by LGX818 single agent in other studies can be enrolled directly in Part II of CLGX818X2102 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.

After careful evaluation of slow enrollment and the BRAF-mutant melanoma treatment landscape, recruitment was permanently halted on 26-Jul-2014.

This recruitment halt was not a consequence of any safety concern and patients who were ongoing in the study continued to be treated as per protocol.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Novartis Investigative Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Novartis Investigative Site
  • Germany
      • Heidelberg, Germany, 69120
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • Switzerland
      • Zuerich, Switzerland, 8091
        • Novartis Investigative Site
  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute Onc Dept

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • locally advanced or metastatic melanoma
  • confirmed BRAF V600 mutation
  • patients naïve to a selective BRAF inhibitor
  • fresh tumor biopsy at baseline, and patient agrees for a mandatory biopsy at the time of relapse
  • life expectancy ≥ 3 months
  • World Health Organization (WHO) Performance Status ≤ 2.

Exclusion Criteria:

  • Previous treatment with RAF-inhibitor
  • Symptomatic or untreated leptomeningeal disease
  • Symptomatic brain metastases.
  • Known acute or chronic pancreatitis
  • Clinically significant cardiac disease
  • AST/SGOT and ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral interventional drug
  • Previous or concurrent malignancy.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Specific exclusion criteria for each treatment arm:

LGX818/MEK162:

History or current evidence of retinal disease History of Gilbert's syndrome.

LGX818/BKM120:

Patients with diabetes mellitus requiring insulin treatment Patient has mood disorders

LGX818/BGJ398:

History and/or current evidence of ectopic mineralization/ calcification Current evidence of corneal disorder/ keratopathy Patients with current evidence of endocrine alteration of calcium/phosphate homeostasis.

History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.

Ionized (i) calcium (Ca) > ULN Serum inorganic phosphorus (Pi) > ULN

LGX818/LEE011 History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: LGX818 single agent
Patients had to have written documentation of a BRAFV600 mutation, which was to have been obtained locally on a fresh tumor biopsy (preferred) or on the most recent archival tumor sample available.
Drug: LGX818
BRAF inhibitor. LGX818 was administered QD orally on a daily schedule (21-day cycles) as a flat-fixed dose and not by body weight or body surface area. LGX818 100 mg capsules and 50 mg capsules.
Other Names:
  • encorafenib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II)
Time Frame: Baseline through study completion (approximately 2 years)

Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define the status of tumors in cancer patients during a specific treatment.

The Overall Response Rate was calculated according to the RECIST criteria, as per investigator assessment.

Per RECIST guidelines:

  • Complete Response (CR) is the Disappearance of all target lesions.
  • Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions.
  • Progressive Disease (PD) is the at least a 20% increase in the sum of diameters of target lesions.
  • Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Baseline through study completion (approximately 2 years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of Dose Limiting Toxicities (DLTs) (Part II)
Time Frame: Baseline through study completion (approximately 2 years)
Incidence of DLTs in Part II of the study was not evaluated due to an inadequate number of patients enrolled in Part II prior to the permanent recruitment halt of this study.
Baseline through study completion (approximately 2 years)
Plasma Concentration and Derived Pharmacokinetic Parameters
Time Frame: Baseline through study completion (approximately 2 years)
Assessment of pharmacokinetic (PK) parameters and plasma concentration was not done due to an inadequate number of patients enrolled in Part II prior to the permanent recruitment halt of this study.
Baseline through study completion (approximately 2 years)
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I)
Time Frame: Baseline through completion of Part I of the study (approximately 2 years)

Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define the status of tumors in cancer patients during a specific treatment.

The Overall Response Rate was calculated according to the RECIST criteria, as per investigator assessment.

Per RECIST guidelines:

  • Complete Response (CR) is the Disappearance of all target lesions.
  • Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions.
  • Progressive Disease (PD) is the at least a 20% increase in the sum of diameters of target lesions.
  • Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Baseline through completion of Part I of the study (approximately 2 years)
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II)
Time Frame: Entry to Part II of the study through study completion (approximately 22 days)

Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define the status of tumors in cancer patients during a specific treatment.

The Overall Response Rate was calculated according to the RECIST criteria, as per investigator assessment.

Per RECIST guidelines:

  • Complete Response (CR) is the Disappearance of all target lesions.
  • Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions.
  • Progressive Disease (PD) is the at least a 20% increase in the sum of diameters of target lesions.
  • Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Entry to Part II of the study through study completion (approximately 22 days)
Molecular Status of Markers Relevant to the RAP/MEK/ERK and PI3K/AKT Pathways
Time Frame: Baseline and at progression with LGX818 single agent treatment
Molecular status was not evaluated due to an inadequate number of patients enrolled in Part II prior to the permanent recruitment halt of this study.
Baseline and at progression with LGX818 single agent treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Array BioPharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2015

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 25, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 28, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 9, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLGX818X2102
  • 2012-004798-17 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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