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Recurrent MelanomaPhase 2NCT02263898

Intermittent LGX818 and MEK162 in Treating Patients With Metastatic Melanoma Who Have BRAFV600 Mutations

A Phase 2 study testing Raf kinase inhibitor LGX818, binimetinib and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IV Melanoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies intermittent dosing of BRAF inhibitor LGX818 (encorafenib) and MEK inhibitor MEK 162 (binimetinib) in treating patients with melanoma that has spread to other parts of the body (metastatic) and have a BRAF V600 mutation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Melanoma, Stage IV Melanoma
What is being tested?
Raf kinase inhibitor LGX818, binimetinib and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jan 2015to Dec 2020
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Signed written informed consent
  • Histologically confirmed diagnosis of metastatic melanoma with the presence of the B-Raf proto-oncogene, serine/threonine kinase (BRAFV600) mutation
  • Eastern Cooperative Oncology Group (ECOG) performance status < 3
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • Hemoglobin (Hgb) >= 9 g/dL without transfusions
  • Platelets (PLT) >= 90 x 10^9/L without transfusions
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  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); patient with liver metastases =< 5 x ULN
  • Total bilirubin =< 2 x ULN, or < 5 ULN if Gilbert’s disease
  • Creatinine =< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) >= 50 mL/min
  • Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Corrected QT (QTc) interval =< 480 ms
  • Able to take oral medications
  • Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up)
  • Negative serum beta (β) human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within 72 hours prior to first dose

Who cannot join

  • Prior exposure to BRAF or MEK inhibitors
  • Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases; however, patient treated with stereotactic radiotherapy, whole brain radiation or surgery are eligible if patient remained without evidence of CNS disease progression >= 4 weeks; patients must be off corticosteroid therapy for >= 2 weeks
  • History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
  • History of retinal degenerative disease
  • History of Gilbert’s syndrome
  • Previous or concurrent malignancy is not an exclusion provided that the other malignancy is considered under control and target lesions from melanoma are clearly defined for response assessment
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  • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening,
  • Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
  • Uncontrolled arterial hypertension despite medical treatment
  • Known positive serology for HIV (human immunodeficiency virus), active hepatitis B, and/or active hepatitis C infection
  • Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
  • Patients taking non-topical medication known to be a strong inhibitor of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); however patients who either discontinue their treatment or switch to another medication at least three days prior to randomization are eligible
  • Any other condition that would, in the Investigator’s judgment, contraindicate the patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc.
  • Patients who have undergone major surgery =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception throughout the study and for 8 weeks after study drug discontinuation; highly effective contraception methods include:
  • Total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening); for female patients on the study, the vasectomized male partner should be the sole partner for that patient
  • Combination of any of the two following (a+b or a+c or b+c)
  • a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception
  • b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • c. Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • In case of use of oral contraception, women should have been stable on the same pill before taking study treatment
  • Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception
  • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
  • Sexually active males unless they use a condom during intercourse while taking the drug and for 8 weeks after stopping treatment and should not father a child in this period; a condom is required to be used also by vasectomized men
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Biomarkers of Durable Response With Intermittent Therapy With LGX818 and MEK162 Combined Therapy in Patients With BRAF Mutant Metastatic Melanoma

This phase II trial studies intermittent dosing of BRAF inhibitor LGX818 (encorafenib) and MEK inhibitor MEK 162 (binimetinib) in treating patients with melanoma that has spread to other parts of the body (metastatic) and have a BRAF V600 mutation. LGX818 and MEK162 may stop the growth of tumor cells by blocking different enzymes needed for cell growth. Giving LGX818 and MEK162 with breaks between each course (intermittently) may help delay the time when tumors become resistant to the drugs.

Read the detailed description

PRIMARY OBJECTIVES:

  1. One year progression free survival (PFS) rate.

SECONDARY OBJECTIVES:

  1. Obtain biopsy samples from patients treated with an intermittent schedule of LGX818 and MEK162 to study adaptive and acquired resistance as well as melanoma evolutionary patterns.

II. Study molecular changes of adaptive resistance and acquired resistance to LGX818 and MEK162 in circulating melanoma cells.

III. Study plasma samples for circulating deoxyribonucleic acid (DNA), microribonucleic acid (microRNA) and protein signatures of adaptive resistance and acquired resistance.

IV. Explore the median progression free survival and overall survival of patients receiving an intermittent schedule of LGX818 and MEK162.

OUTLINE:

Patients receive LGX818 orally (PO) once daily (QD) and MEK162 PO twice daily (BID) continuously for 8 weeks, followed by intermittent dosing in subsequent cycles (3 weeks off therapy, 5 weeks on therapy). Cycles repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Being tested
Raf kinase inhibitor LGX818, binimetinib, laboratory biomarker analysis
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Raf kinase inhibitor LGX818Drug

    Also called LGX818

    Given PO

  • binimetinibDrug

    Also called ARRY-162, ARRY-438162, MEK inhibitor ARRY-438162, MEK162

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02263898
Study groupRoleWhat they receive
Treatment (LGX818, MEK162)ExperimentalPatients receive LGX818 PO QD and MEK162 PO BID continuously for 8 weeks followed by intermittent dosing in subsequent cycles (3 weeks off therapy, 5 weeks on therapy). Cycles repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Raf kinase inhibitor LGX818; Drug: binimetinib; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PFS rate

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2014 (estimated)
  2. Study startJan 2015
  3. Primary completionDec 2019 (estimated)
  4. Study completionDec 2020 (estimated)

Why it stopped: closed without enrollment

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02263898
Sponsor's protocol ID
14-000616
Other IDs
NCI-2014-01971, 14-000616, P01CA168585
Status last verified
Dec 2016
First submitted
8 Oct 2014
Last updated
27 Jul 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Raf kinase inhibitor LGX818, binimetinib and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IV Melanoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

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 14 inclusion and 31 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: withdrawn, as of the sponsor's last update on 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

PFS rate (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02263898.

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 27 Jul 2020.

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