Neoadjuvant Dabrafenib + Trametinib for AJCC Stage IIIB-C BRAF V600 Mutation Positive Melanoma

NCT01972347 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 200332
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single centre, phase II study of neoadjuvant drug treatment with dabrafenib + trametinib in patients with resectable American Joint Committee on Cancer (AJCC) Stage IIIB-C BRAF V600 mutation positive melanoma. The main aim of this study is to find out if giving of a new combined drug treatment to patients with melanoma that has spread to the lymph nodes BEFORE they have surgery, will result in improved clinical and pathological response of the melanoma tissue after 12 weeks treatment.

Conditions

Melanoma

Keywords

Melanoma; Cutaneous melanoma; Malignant melanoma; Stage III B / C melanoma; Neoadjuvant treatment; Pyrexia; Biomarkers; Dabrafenib; Trametinib

Outcome Measures

Primary Outcomes (1)

• The proportion of viable melanoma tissue, compared to baseline, in dissected lymph node and / or in-transit tumour tissue after 12 weeks of neoadjuvant treatment.

  The proportion of viable melanoma tissue, compared to baseline, in dissected lymph node and / or in-transit tumour tissue after 12 weeks of neoadjuvant treatment.

  12 weeks

Secondary Outcomes (9)

• Effects of neoadjuvant study treatment on surgical outcomes after complete lymph node and / or in-transit disease dissection.

  12 weeks

• Effects of study treatment on host immune response in tumour tissue and peripheral blood.

  12 weeks

• Correlation of pyrexia episodes and signs with baseline melanoma disease burden (number and size of lymph nodes), RECIST response, pathological response, immune related changes in tumour tissue and peripheral blood.

  52 weeks

• Description of specific blood and serum changes that occur with pyrexia.

  52 weeks

• Relapse free survival

  52 weeks plus the time when 70% of patients have died

Study Arms (1)

Dabrafenib and Trametinib

EXPERIMENTAL

Dabrafenib 150mg bid orally and Trametinib 2mg od orally for 52 weeks

Drug: Dabrafenib; Drug: Trametinib

Interventions

Dabrafenib DRUG

Patients will receive neoadjuvant treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 12 weeks. Patients will then have complete lymph node dissection and will continue on maintenance treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 40 weeks.

Also known as: GSK2118436

Dabrafenib and Trametinib

Trametinib DRUG

Patients will receive neoadjuvant treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 12 weeks. Patients will then have complete lymph node dissection and will continue on maintainance treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 40 weeks.

Also known as: GSK1120212

Dabrafenib and Trametinib

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Histologically confirmed AJCC Stage IIIB or IIIC (Tx, T1-4, N1b, N2b, N2c, N3, Mo) cutaneous melanoma or unknown primary determined to be BRAF V600 mutation positive, with sufficient nodal or in-transit disease to enable biopsies prior to surgery.Patients must have disease that is measurable per RECIST version 1.1
• Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Adequate baseline organ function
• Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 4 months after the last dose of study treatment
• Men with any female partner of childbearing potential must agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 4 months after the last dose of study treatment

You may not qualify if:

• Known mucosal or ocular melanoma or any unresectable in-transit metastases
• Evidence of distant metastatic disease on screening evaluation
• Prior anti-cancer treatment for melanoma (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, investigational treatment or radiotherapy). Prior surgery for melanoma is allowed.
• Taken an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to commencing study treatment.
• Current or expected use of a prohibited medication(s)
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO)
• Known HIV
• A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency
• History of another malignancy or a concurrent malignancy except:
• Patients who have been disease-free for 3 years and have a life expectancy of \> 5 years;
• Patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas.
• A history or evidence of cardiovascular risk including any of the following: a. QT interval corrected for heart rate using the Bazett's formula ≥480 msec or ≥ 450 msec for patients with bundle branch block; b. History or evidence of current clinically significant uncontrolled arrhythmias; c. History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to commencement of study treatment; d. History or evidence of current ≥ Class II congestive heart failure; e. Abnormal cardiac valve morphology documented by echocardiogram which in the opinion of the investigator could interfere with the patient's safety.
• f. Treatment refractory hypertension defined as a blood pressure of systolic \> 140 mm Hg and/or diastolic \> 90 mm Hg which cannot be controlled by anti-hypertensive therapy.
• A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
• Any serious or unstable pre-existing medical conditions (aside from the malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the treating clinician, could interfere with the patient's safety, obtaining informed consent, or compliance with study procedures.

Sponsors & Collaborators

• Melanoma Institute Australia: lead

Study Sites (1)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

Location

Related Publications (2)

• Long GV, Saw RPM, Lo S, Nieweg OE, Shannon KF, Gonzalez M, Guminski A, Lee JH, Lee H, Ferguson PM, Rawson RV, Wilmott JS, Thompson JF, Kefford RF, Ch'ng S, Stretch JR, Emmett L, Kapoor R, Rizos H, Spillane AJ, Scolyer RA, Menzies AM. Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB-C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial. Lancet Oncol. 2019 Jul;20(7):961-971. doi: 10.1016/S1470-2045(19)30331-6. Epub 2019 Jun 3.

  PMID: 31171444 DERIVED

• Kim HY, Duong JK, Gonzalez M, Long GV, Menzies AM, Rizos H, Lim SY, Lee J, Boddy AV. Pharmacokinetic and cytokine profiles of melanoma patients with dabrafenib and trametinib-induced pyrexia. Cancer Chemother Pharmacol. 2019 Apr;83(4):693-704. doi: 10.1007/s00280-019-03780-y. Epub 2019 Jan 19.

  PMID: 30661097 DERIVED

Related Links

• Melanoma Institute Australia - current research projects

MeSH Terms

Conditions

Melanoma; Fever

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; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Georgina Long

  Melanoma Institute Australia

  STUDY DIRECTOR

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: June 17, 2013
• First Posted: October 30, 2013
• Study Start: October 1, 2014
• Primary Completion: May 4, 2017
• Study Completion: May 1, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)