MelanomaPhase 2LOGICNCT01820364
LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma
A Phase 2 study testing LGX818 in people with Melanoma, run by Array BioPharma at 6 sites in 6 countries.
Trial summary
The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- LGX818
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 6 sitesin 6 countries
- Study dates
- Nov 2013to Mar 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 19Show fewer
- 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.
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
United States1 site
Sarah Cannon Research Institute Onc Dept
Nashville, Tennessee, 37203
About this study
Official title: 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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- LGX818
- Keywords
- open-label study, BRAF inhibitor, LGX818, MEK1620, MAPK1/2 inhibitor, Pi3K inhibitor, FGFR, c-Met, CDK4/6, metastatic melanoma, BRAF, V600
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LGX818Drug
Also called encorafenib
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.
| Study group | Role | What they receive |
|---|---|---|
| LGX818 single agent | Experimental | 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. Receives: Drug: LGX818 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II)
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.
Measured: Baseline through study completion (approximately 2 years)
Secondary outcomes (5)
Incidence of Dose Limiting Toxicities (DLTs) (Part II)
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.
Measured: Baseline through study completion (approximately 2 years)
Plasma Concentration and Derived Pharmacokinetic Parameters
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.
Measured: Baseline through study completion (approximately 2 years)
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I)
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.
Measured: 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)
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.
Measured: 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
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.
Measured: Baseline and at progression with LGX818 single agent treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2013 (estimated)
- Study startNov 2013
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: Study was withdrawn due to scientific and business considerations.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Array BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Array BioPharma, Study director, 303-381-6604
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01820364
- Sponsor's protocol ID
- CLGX818X2102
- Other IDs
- 2012-004798-17
- Acronym
- LOGIC
- Status last verified
- Nov 2016
- First submitted
- 25 Mar 2013
- Last updated
- 9 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01820364
- Acronym / sponsor ID
- LOGIC / CLGX818X2102
- Conditions
- Melanoma
- Keywords
- open-label study, BRAF inhibitor, LGX818, MEK1620, MAPK1/2 inhibitor, Pi3K inhibitor, FGFR, c-Met
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was withdrawn due to scientific and business considerations.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Array BioPharmaIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 28 Mar 2013 (estimated)
- Results
- Posted 9 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the Phase II CLGX818X2102 study is to assess the anti-tumor activity of LGX818 in combination with selected agents.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LGX818 single agent | Experimental | Drug: LGX818Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- Previous treatment with RAF-inhibitor
- Symptomatic or untreated leptomeningeal disease
- Symptomatic brain metastases.
- Known acute or chronic pancreatitis
- Clinically significant cardiac disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LGX818Also: encorafenibBRAF 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. | Drug | LGX818 single agent |
Primary outcome
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.
5 secondary outcomes
Incidence of Dose Limiting Toxicities (DLTs) (Part II)
Time frame: Baseline through study completion (approximately 2 years)
Plasma Concentration and Derived Pharmacokinetic Parameters
Time frame: 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)
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)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Array BioPharma study director
303-381-6604
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LGX818 in people with Melanoma, run by Array BioPharma at 6 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia, Canada, Germany, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2017.