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Recurrent MelanomaPhase 2NCT02296112

Trametinib in Treating Patients With Advanced Melanoma With BRAF Non-V600 Mutations

A Phase 2 study testing trametinib, laboratory biomarker analysis and pharmacological study in people with Recurrent Melanoma and Stage IIIB Melanoma, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies trametinib in treating patients with melanoma with v-Raf murine sarcoma viral oncogene homolog B (BRAF) non-V600 mutations that has spread to other places in the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
trametinib, laboratory biomarker analysis and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
4 sitesUnited States
Study dates
Jan 2015to 16 Apr 2021
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

  • Signed written informed consent
  • Histologically or cytologically confirmed diagnosis of melanoma
  • BRAF mutation in loci other than V600 (BRAF nonV600 MUT) or BRAF fusion detected by genetic testing of the primary tumor or regional/distant metastasis
  • Subjects must provide either a fresh or archived tumor sample for correlative study analyses
  • For subjects with melanoma, archived or freshly biopsied tumor tissue (preferred) must be obtained prior to enrollment. Tissue shipment tracking information should be provided before administration of study treatment is initiated. However, if shipping will be delayed and tissue shipment tracking information is unavailable, study drug may be administered prior to tissue receipt pending discussion with principal investigator.
  • Measurable disease (i.e., present with at least one measurable lesion per Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1)
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  • All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values) must be =< grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0) at the time of randomization. Subjects with endocrinopathies (e.g. hypopituitarism, hypothyroidism, hypoadrenalism) caused by immune therapies currently on adequate hormone replacement WILL be permitted.
  • Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to use effective contraception
  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception
  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count (ANC) > or = 1.0 × 10^9/L
  • Hemoglobin > or = 9 g/dL
  • Platelet count > or = 75 x 10^9/L
  • Prothrombin time (PT)/international normalized ratio (INR)* = or < 1.3 x upper limit of normal (ULN)
  • Subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to randomization; PT and partial thromboplastin time (PTT) > 1.5 x ULN are permitted in these subjects
  • PTT =or < 1.3 x ULN
  • Albumin >or = 2.5 g/dL
  • Total bilirubin = or < 1.5 x ULN
  • Alanine aminotransferase (ALT) = or < 2.5 x ULN
  • Creatinine = or < 1.5 ULN or calculated creatinine clearance* > or = 50 mL/min
  • Calculate creatinine clearance using standard Cockcroft-Gault formula; creatinine clearance must be > or = 50 mL/min to be eligible
  • Left ventricular ejection fraction (LVEF) > or = lower limit of normal (LLN) by echocardiogram (ECHO)

Who cannot join

  • No prior therapy with inhibitors affecting the mitogen-activated protein kinase (MAPK) pathways at any level (BRAF, mitogen-activated protein [MAP]/extracellular signal-related kinase [ERK] kinase [MEK], neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS], ERK inhibitors) for unresectable stage IIIC or stage IV (metastatic) melanoma; no limit to other therapies (immunotherapy or chemotherapy); prior systemic treatment in the adjuvant setting is allowed; (note: ipilimumab treatment must end at least 8 weeks prior to study day 1)
  • BRAFV600 mutation positive
  • NRAS codon 12, 13, or 61 mutation
  • Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to study day 1, or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to study day 1
  • Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to study day 1
  • Current use of a prohibited medication as described
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  • History of another malignancy
  • Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected, non-melanoma skin cancer, or subjects with indolent second malignancies are eligible. T1a melanoma and melanoma in situ are permitted. Consult Medical Monitor if unsure whether second malignancies meet requirements specified above.
  • Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures
  • Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV infection will be permitted)
  • History of leptomeningeal disease or spinal cord compression secondary to metastasis
  • Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery and the disease has been confirmed stable (i.e., no increase in lesion size) for at least 6 weeks with two consecutive magnetic resonance imaging (MRI) scans using contrast prior to study day 1; enzyme inducing anticonvulsants are not allowed while patients are on study treatment
  • A history or evidence of cardiovascular risk including any of the following:
  • A QT interval corrected for heart rate using the Bazett's formula (QTc) > or = 480 msec
  • A history or evidence of current clinically significant uncontrolled arrhythmias
  • Exception: subjects with atrial fibrillation controlled for > 30 days prior to study day 1
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study day 1
  • A history or evidence of current >= class I congestive heart failure as defined by the New York Heart Association (NYHA) guidelines
  • Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
  • Patients with intra-cardiac defibrillators or permanent pacemakers
  • Known cardiac metastases
  • A history or current evidence of retinal vein occlusion (RVO) including:
  • History of RVO or
  • Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO such as:
  • Evidence of new optic disc cupping
  • Evidence of new visual field defects
  • Intraocular pressure > 21 mmHg as measured by tonography
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO)
  • History of interstitial lung disease or pneumonitis
  • Females who are pregnant or nursing

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase II Open-Label, Two-Arm Study of the MEK Inhibitor, Trametinib, to Investigate the Safety and Anti-Cancer Activity in Subjects With Melanoma With BRAF Non-V600 Mutations

This phase II trial studies trametinib in treating patients with melanoma with v-Raf murine sarcoma viral oncogene homolog B (BRAF) non-V600 mutations that has spread to other places in the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the clinical efficacy of trametinib in advanced BRAF nonV600mutation (MUT) melanoma ("high activity" group).

SECONDARY OBJECTIVES:

  1. To characterize the safety of trametinib. II. To evaluate the progression-free survival (PFS) and overall survival (OS) of trametinib in advanced BRAF nonV600MUT melanoma.

TERTIARY OBJECTIVES:

  1. To determine the clinical efficacy of trametinib in advanced BRAF nonV600MUT melanoma ("low activity/unknown" group).

II. Identify mechanisms of resistance to trametinib in this patient population.

OUTLINE:

Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days.

Being tested
trametinib, laboratory biomarker analysis, pharmacological study
Medical subject headings
Melanoma

What participants receive

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

  • trametinibDrug

    Also called GSK1120212, JTP-74057, Mekinist

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT02296112
Study groupRoleWhat they receive
Treatment (trametinib)ExperimentalPatients receive trametinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: trametinib; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. Overall Response Rate in "High Affinity" Group

    Per RECIST criteria version (v.) 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions.

    Measured: Up to 12 months

Secondary outcomes (6)

  1. Progression-Free Survival All Patients

    Progression of disease as defined by RECIST 1.1 criteria will be reported. Time from on treatment to progression or death (whichever comes first). For those did not progress or die, they were censored at the last follow up or off study date(if they do not have a last date of follow up).

    Measured: On-study date to lesser of date of progression or date of death from any cause (assessed up to 3 years)

  2. Duration of Response in "High Affinity" Group

    Estimated probable duration from date of objective response to date of disease progression, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under RECIST v1.1 as >= 20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

    Measured: Date of first partial or complete response as defined by RECIST 1.1 criteria to date of progression up to 3 years

  3. Clinical Benefit (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD]) Per RECIST v. 1.1 in "High Affinity" Group

    Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions.

    Measured: Up to 12 months

  4. Overall Survival

    Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring.

    Measured: On-study date to date of death from any cause (assessed up to 3 years)

  5. Number of Patients With Each Worst-Grade Toxicity

    Safety profile shown by count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per National Cancer Institute (NCI) common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death.

    Measured: On-study date to 30 days following final dose of study drug, up to 3 years

  6. Overall Response Rate in "Low Affinity" Group

    Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions.

    Measured: Up to 12 months

Timeline

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

  1. First posted20 Nov 2014 (estimated)
  2. Study startJan 2015
  3. Primary completionAug 2018
  4. Study completion16 Apr 2021

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
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02296112
Sponsor's protocol ID
VICC MEL 1457
Other IDs
NCI-2014-02185, MEL1457, GSK1120212, VICC MEL 1457, P30CA068485
Status last verified
May 2021
First submitted
17 Nov 2014
Last updated
28 May 2021
Data monitoring committee
Yes

Publications

  • Nebhan CA, Johnson DB, Sullivan RJ, Amaria RN, Flaherty KT, Sosman JA, Davies MA. Efficacy and Safety of Trametinib in Non-V600 BRAF Mutant Melanoma: A Phase II Study. Oncologist. 2021 Sep;26(9):731-e1498. doi: 10.1002/onco.13795. Epub 2021 May 4.

    PubMed 33861486

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing trametinib, laboratory biomarker analysis and pharmacological study in people with Recurrent Melanoma and Stage IIIB Melanoma, run by Vanderbilt-Ingram Cancer Center at 4 sites 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 23 inclusion and 30 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: finished, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

Yes. Results are posted in the registry (first posted 8 Aug 2019). 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?

Overall Response Rate in "High Affinity" Group (time frame: Up to 12 months). 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 NCT02296112, which also lists 1 linked publication.

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 28 May 2021.

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