Dabrafenib and Trametinib Before and After Surgery in Treating Patients With Stage IIIB-C Melanoma With BRAF V600 Mutation

NCT02231775 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2014-0409NCI-2014-01969
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase II trial focused on how dabrafenib and trametinib before and after surgery works in treating patients with stage IIIB-C melanoma that has a specific mutation in the BRAF gene. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dabrafenib and trametinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving dabrafenib and trametinib after surgery may kill any remaining tumor cells.

Conditions

Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival (RFS)

  RFS will be compared between patients with a pathologic complete response (pCR) and patients without a pCR using a two-sided log-rank test.

  Up to 1 year

Secondary Outcomes (4)

• Overall survival (OS)

  Up to 1 year

• Complete pathologic response

  Up to 1 year

• Incidence of adverse events

  Up to 1 year

• Markers predictive of response collected by serial blood draws and biopsies

  Up to 1 year

Study Arms (1)

Treatment (dabrafenib, trametinib, surgery)

EXPERIMENTAL

Patients receive dabrafenib PO BID and trametinib PO QD for 8 weeks. After completion of 8 weeks of dabrafenib and trametinib, patients undergo surgery. Approximately 1 week after surgery, patients receive dabrafenib PO BID and trametinib PO QD for 44 additional weeks in the absence of disease progression or unacceptable toxicity.

Drug: Dabrafenib; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery; Drug: Trametinib

Interventions

Dabrafenib DRUG

Given PO

Also known as: BRAF Inhibitor GSK2118436, GSK-2118436, GSK-2118436A, GSK2118436

Treatment (dabrafenib, trametinib, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dabrafenib, trametinib, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (dabrafenib, trametinib, surgery)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212

Treatment (dabrafenib, trametinib, surgery)

Eligibility Criteria

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

You may qualify if:

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• Patients must have histologically or cytologically confirmed stage IIIB/C melanoma by American Joint Committee on Cancer (AJCC) version 7; the definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at Multidisciplinary Tumor Conference attended by melanoma medical and surgical oncology staff; resectable tumors are defined as having no significant vascular, neural or bony involvement; only cases where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable
• Multicenter sites: confirmation of diagnosis via histology or cytology will be made by the local site pathologist; likewise, resectability determination will be made by the site's multidisciplinary team
• Patients must be medically fit enough to undergo surgery as determined by the surgical oncology team
• BRAF mutation-positive melanoma (V600E or V600K) based on report from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
• Patients must have measurable disease, defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin \>= 9.5 g/dL
• Platelets \>= 100 x 10\^9/L
• Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) =\< 1.5 x upper limit of normal (ULN)
• Total bilirubin =\< 1.5 x ULN (isolated bilirubin \> 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Albumin \>= 2.5 g/dL
• Creatinine =\< 1.5 x ULN OR calculated creatinine clearance \>= 50 mL/min OR 24-hour urine creatinine clearance \>= 50 mL/min

You may not qualify if:

• Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug within 28 days
• Current use of a prohibited medication or requires any of these medications during treatment with study drug
• Prior BRAF or mitogen-activated protein kinase kinase (MEK) directed therapy
• Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years
• Any major surgery within the last 3 weeks
• History of central serous retinopathy (CSR) or retinal vein occlusion (RVO), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs
• Brain metastases or bone metastases; patients with brain metastases must have received treatment for them (resection or stereotactic radiosurgery \[SRS\]) and these metastatic foci must be stable for 8 weeks prior to starting study drug
• Corrected QT (QTc) interval \>= 480 msec (\>= 500 msec for subjects with bundle branch block)
• Uncontrolled arrhythmias
• Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• Pregnant or lactating female
• Unwillingness or inability to follow the procedures required in the protocol
• Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
• Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

• Amaria RN, Prieto PA, Tetzlaff MT, Reuben A, Andrews MC, Ross MI, Glitza IC, Cormier J, Hwu WJ, Tawbi HA, Patel SP, Lee JE, Gershenwald JE, Spencer CN, Gopalakrishnan V, Bassett R, Simpson L, Mouton R, Hudgens CW, Zhao L, Zhu H, Cooper ZA, Wani K, Lazar A, Hwu P, Diab A, Wong MK, McQuade JL, Royal R, Lucci A, Burton EM, Reddy S, Sharma P, Allison J, Futreal PA, Woodman SE, Davies MA, Wargo JA. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 2018 Feb;19(2):181-193. doi: 10.1016/S1470-2045(18)30015-9. Epub 2018 Jan 18.

  PMID: 29361468 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; 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

Study Officials

• Rodabe N Amaria

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 4, 2014
• Study Start: October 22, 2014
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

US (1)