NCT02196181|Active Not RecruitingPhase 2

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

A Randomized Phase II Trial of Intermittent Versus Continuous Dosing of Dabrafenib (NSC-763760) and Trametinib (NSC-763093) in BRAF V600E/K Mutant Melanoma

National Cancer Institute (NCI)ClinicalTrials.gov

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4 other identifiers

NCI-2014-01470S1320U10CA032102U10CA180888

Study Type

interventional

Target

280

Locations

1 country

Sites

754

Timeline

RegisteredJul 2014

StartedSep 2014

CompletionMar 2027

Brief Summary

This phase II trial compares the effect of dabrafenib and trametinib given continuously to given with a break in treatment (intermittent) in treating patients with stage III-IV melanoma that cannot be removed by surgery and contains a B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dabrafenib and trametinib with intermittent dosing may be as effect as when given continuously in treating patients with stage III-IV melanoma with a BRAF mutation that cannot be removed by surgery.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

280

participants targeted

Target at P75+ for phase_2

Timeline

9mo left

Started Sep 2014

Longer than P75 for phase_2

Geographic Reach

1 country

754 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

12.5 years study duration

Study Progress94%

Sep 2014Mar 2027

First Submitted

Initial submission to the registry

July 18, 2014

Completed

3 days until next milestone

First Posted

Study publicly available on registry

July 21, 2014

Completed

2 months until next milestone

Study Start

First participant enrolled

September 19, 2014

Completed

12.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2027

Last Updated

May 29, 2026

Status Verified

March 1, 2026

Enrollment Period

12.5 years

First QC Date

July 18, 2014

Last Update Submit

May 28, 2026

Conditions

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

Outcome Measures

Primary Outcomes (1)

Progression-free survival (PFS)
Testing of the superiority of intermittent dosing of dabrafenib and trametinib compared to continuous dosing with these two same agents will be based on progression-free survival. Stratified Cox regression models stratified by stratification factors will be used for all analyses.
Measured from date of randomization, assessed up to 5 years

Secondary Outcomes (3)

Overall survival
Up to 5 years
Response rates
Up to 5 years
Rates of fever
Up to 5 years

Other Outcomes (3)

Molecular events leading to reactivation of the MAPK pathway
Up to 5 years
Change in biomarkers associated with PFS of archived tissue
Baseline up to 5 years
Interaction between baseline biomarkers and treatment arm
Baseline up to 5 years

Study Arms (2)

Arm I (continuous dosing)

EXPERIMENTAL

Patients receive dabrafenib PO BID and trametinib PO QD on days 1-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, ECHO or MUGA on study.

Procedure: Biospecimen CollectionProcedure: Computed TomographyDrug: Dabrafenib MesylateProcedure: Echocardiography TestProcedure: Multigated Acquisition ScanProcedure: Positron Emission TomographyDrug: Trametinib Dimethyl Sulfoxide

Arm II (intermittent dosing)

EXPERIMENTAL

Patients receive dabrafenib PO BID and trametinib PO QD on days 1-7 and 29-56 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT scans in week 1 of cycle 2 and at off treatment follow up prior to progression. Additionally, patients undergo blood sample collection, ECHO or MUGA on study.

Interventions

Dabrafenib MesylateDRUG

Given PO

Also known as: Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar

Arm I (continuous dosing)Arm II (intermittent dosing)

Positron Emission TomographyPROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm I (continuous dosing)Arm II (intermittent dosing)

Computed TomographyPROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (continuous dosing)Arm II (intermittent dosing)

Multigated Acquisition ScanPROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm I (continuous dosing)Arm II (intermittent dosing)

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm I (continuous dosing)Arm II (intermittent dosing)

Echocardiography TestPROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm I (continuous dosing)Arm II (intermittent dosing)

Trametinib Dimethyl SulfoxideDRUG

Given PO

Also known as: Mekinist, Meqsel, Spexotras

Arm I (continuous dosing)Arm II (intermittent dosing)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

STEP 1: REGISTRATION
Patients must have histologically or cytologically confirmed stage IV or unresectable stage III BRAF V600E or BRAF V600K mutant melanoma
Patients must have BRAF V600E or BRAF V600K mutation identified by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; acceptable analytic techniques include but are not restricted to DNA sequencing, pyrosequencing, polymerase chain reaction (PCR), melting point assays, and immunohistochemistry
Contrast-enhanced CT scans of the neck, chest, abdomen and pelvis are required; a whole body PET/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the neck, chest, abdomen and pelvis; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1)
Patients must not have received a prior BRAF or MEK inhibitor
Patients with a history of brain metastases are eligible if the patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 7 days prior to registration
Patients must not have received any anti-cancer drug within 28 days prior to registration, and must not have received any nitrosoureas or mitomycin C within 42 days prior to registration
Patients must not have received any major surgery or immunotherapy within 28 days prior to registration
Patients must not have any unresolved toxicity greater than National Cancer Institute (NCI)-CTCAE version (v) 4.0 grade 1 from previous anti-cancer therapy except alopecia within 7 days prior to registration
Patients must be age \>= 18 years of age
Absolute neutrophil count (ANC) \>= 1,200/ul (obtained within 28 days prior to registration)
Platelets \>= 100,000/ul (obtained within 28 days prior to registration)
Hemoglobin \>= 9 g/dL (obtained within 28 days prior to registration)
Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (or =\< 2.5 x upper limit of normal \[ULN\] with Gilbert's syndrome) (obtained within 28 days prior to registration)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (or \< 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration)
+35 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (754)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC