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

NCT02296112 | Completed Phase 2 Results DMC

• 5 other identifiers: VICC MEL 1457NCI-2014-02185MEL1457GSK1120212P30CA068485
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Recurrent Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (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.

  Up to 12 months

Secondary Outcomes (6)

• Progression-Free Survival All Patients

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

• Duration of Response in "High Affinity" Group

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

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

  Up to 12 months

• Overall Survival

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

• Number of Patients With Each Worst-Grade Toxicity

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

Other Outcomes (3)

• Duration of Response in "Low Affinity" Group

  Up to 3 years

• Clinical Benefit (CR + PR + SD) Per RECIST v. 1.1 in "Low Affinity" Group

  Up to 12 months

• Molecular Characteristics of Patient Samples, Including Archival Samples

  Up to 3 years

Study Arms (1)

Treatment (trametinib)

EXPERIMENTAL

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

Drug: trametinib; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, Mekinist

Treatment (trametinib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (trametinib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (trametinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (4)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 33861486 DERIVED

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Melanoma

Interventions

trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Douglas Johnson, MD
• Organization: Vanderbilt University Medical Center

douglas.b.johnson@vumc.org

(615) 936-8422

Study Officials

• Douglas Johnson

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 20, 2014
• Study Start: January 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: April 16, 2021
• Last Updated: May 28, 2021
• Results First Posted: August 8, 2019

Record last verified: 2021-05

Locations

US (4)