Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2015-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase II trial studies how well giving dabrafenib alone and in combination with trametinib before surgery works in treating patients with advanced melanoma that can be removed by surgery. Studying samples of tumor tissue in the laboratory from patients receiving dabrafenib and trametinib may help doctors learn more about the effects of these drugs on cells and help identify biomarkers that determine which patients will respond to these drugs best.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT02231775

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

ACTIVE_NOT_RECRUITING PHASE2

LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) and the MEK Inhibitor (Trametinib) in Unresectable Stage III and Stage IV BRAF Mutant Melanoma; Correlation of Resistance With the Kinome and Functional Mutations

NCT01726738

Stage III Melanoma Stage IV Melanoma Unresectable Melanoma +1 more

COMPLETED PHASE2

Testing Two Different Treatment Schedules of Dabrafenib and Trametinib for Skin Cancer Which Has Spread

NCT02196181

Stage III Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Unresectable Melanoma

ACTIVE_NOT_RECRUITING PHASE2

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

NCT01584648

Melanoma

COMPLETED PHASE3

Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

NCT02097225

BRAF V600E Mutation Present BRAF V600K Mutation Present Metastatic Malignant Solid Neoplasm +7 more

TERMINATED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. To identify markers of intrinsic resistance to v-Raf murine sarcoma viral oncogene homolog B1 (B-RAF) targeted therapy in B-RAF mutation-positive melanoma.

SECONDARY OBJECTIVES:

I. To determine if intrinsic resistance can be reversed by mitogen activated protein kinase (MEK) targeted therapy and to identify biomarkers that correlate with this response.

II. To evaluate the feasibility of pre-surgical targeted therapy and serial tumor biopsies in patients with advanced, operable melanoma to determine if this model can be used to evaluate novel combinations of molecular targeted therapy in the future.

TERTIARY OBJECTIVES:

I. To determine if pre-surgical B-RAF and MEK targeted therapy is active and well tolerated in patients with advanced, operable melanoma. These findings may be used to support clinical trials in un-resectable, B-RAF mutation-positive melanoma.

OUTLINE:

Patients receive dabrafenib orally (PO) twice daily (BID) on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues until the day prior to surgery in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 months.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Recurrent Melanoma Stage IIB Melanoma (Locally Advanced) Stage IIC Melanoma (Locally Advanced) Stage IIIA Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma (Limited, Resectable)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dabrafenib and Trametinib

Patients receive dabrafenib PO BID on days 1-28 adding trametinib on days 15-28 followed by surgery on days 28-30. Treatment continues in the absence of unacceptable toxicity.

Group Type EXPERIMENTAL

dabrafenib

Intervention Type DRUG

150 mg given PO

trametinib

Intervention Type DRUG

2 mg given PO

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

dabrafenib

150 mg given PO

Intervention Type DRUG

trametinib

2 mg given PO

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

BRAF inhibitor GSK2118436 GSK2118436 GSK1120212

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Signed written informed consent
* Patients with locally-or regionally advanced melanoma being considered for resection of the lesion(s) for local-regional control and potential cure

* Patients with limited, resectable metastatic disease (three or fewer lesions) are eligible if surgical resection is considered to be the best therapeutic option
* Patients with AJCC clinical stage IIb-IV disease at initial diagnosis, or patients with melanoma of any stage with advanced local or regional recurrence, with or without limited resectable metastatic disease, would be eligible
* B-RAF V-600 mutation positive by snapshot molecular analysis

* Individuals with B-RAF V-600 mutations other than V600E are eligible
* Measurable disease, i.e. presenting with at least one measurable lesion per Response Evaluation Criteria in Solid tumors (RECIST) 1.1
* All prior treatment related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) =\< Grade 1 at the time of enrollment
* Adequate baseline organ function defined by the criteria below:

* Absolute Neutrophil Count (ANC) \>= 1.5 X 10\^9/L
* Platelet Count \>= 60 X 10\^9/L
* Hemoglobin \>= 9 g/dl
* Creatinine =\< 2 mg/dl
* Aspartate aminotransferase (AST) =\< 100 U/L
* Alanine aminotransferase (ALT) =\< 100 U/L
* Alkaline Phosphatase =\< 380 U/L
* Total Bilirubin =\< 2.0 mg/dl
* Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception during the study and for 7 days following the last dose of study treatment
* Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from 1 day prior to administration of the first dose of study treatment until 7 days after the last dose of study treatment

Exclusion Criteria

* ECOG Performance Status \> 2
* Lactating female
* Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
* Any serious medical condition that would render the patient unable to undergo surgical resection or would limit life expectancy to less than 1 year
* Any prohibited medication
* Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment
* A known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK-2118436 (dabrafenib) or GSK-1120212 (trametinib) or excipient that contraindicates their participation
* Patients with a history of severe cardiovascular disease as defined:

* Symptomatic or uncontrolled cardiac arrhythmias
* Treatment refractory hypertension, defined as a systolic blood pressure \> 160mm Hg and/or diastolic \> 100 mmHg which cannot be controlled by antihypertensive therapy.
* Current ≥ NYHA Class II congestive heart failure
* History of myocardial infarction or unstable angina within 6 months prior to study entry.
* History of stroke or TIA within 6 months prior to study entry
* QTc ≥ 480 msec
* Cardiac valvular disease ≥ grade 2.
* Patients with a history of interstitial lung disease or interstitial pneumonitis
* A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
* History of another active malignancy within the past 5 years, or any malignancy with a confirmed activating RAS mutation. Please note that prospective RAS mutation testing is not required, however, if results of previous RAS testing are known, they must be used in assessing eligibility. Subjects with a history of completely resected non-melanoma skin cancer are eligible.
* A history or current evidence/risk of retinal vein occlusion (RVO) or CSR including:
* a. Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or
* b. Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as:

* i. Evidence of new optic disc cupping;
* ii. Evidence of new visual field defects on automated perimetry;
* iii. Intraocular pressure \>21 mmHg as measured by tonography.

Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No