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Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02143050
Recruitment Status : Recruiting
First Posted : May 20, 2014
Last Update Posted : November 23, 2016
Sponsor:
Collaborator:
University of Louisville
Information provided by (Responsible Party):
James Graham Brown Cancer Center

Study Description
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Brief Summary:
The main purpose is to evaluate the clinical response, safety and survival of the FDA approved drugs Dabrafenib, Trametinib in combination with Metformin. Investigators hypothesize that the combination of an FDA approved non toxic dose of oral Metformin with the B-Raf inhibitor, Dabrafenib and the MEK inhibitor, Trametinib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Dabrafenib Drug: Trametinib Drug: Metformin Phase 1 Phase 2

Detailed Description:
The study will be a single-arm, single center, uncontrolled phase I/II trial to estimate the safety of the combined treatments and then estimate the efficacy in terms of objective response rate in patients with stage IIIC and Stage IV melanoma treated with dabrafenib/trametinib and metformin.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Dabrafenib, Trametinib and Metformin Administered to Unresectable Stage IIIC and Stage IV BRAF V600E + Melanoma Patients
Study Start Date : September 2014
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dabrafenib, Trametinib and Metformin
Dabrafenib 150 mg PO BID until progression or unacceptable toxicity. Trametinib 2 mg PO QD until progression or unacceptable toxicity. Metformin 500 mg PO BID x 2 weeks, then 850 mg PO BID until progression or unacceptable toxicity.
 Drug: Dabrafenib
Other Name: Tafinlar

Drug: Trametinib
Other Name: Mekinist

Drug: Metformin
Other Name: Glucophage


Outcome Measures
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Primary Outcome Measures :
  1. Observation of two CTCAE drug related grade 4 toxicities in six patients. [ Time Frame: Duration of phase I portion, approxiately 6 months ]
    During phase I, six patients will be enrolled and monitored for toxicities. If drug related deaths occur or more than two drug related CTCAE grade 4 toxicities occur the trial will be suspended. Phase II will estimate the efficacy of the drugs, enrolling 20 patients during stage 1 with an upper limit of 39 for the 2nd stage.

  2. Clinical Response Rate [ Time Frame: 6 years ]
    Phase II will study the efficacy of the drugs enrolling 20 patients during stage I with an upper limit of 39 for the 2nd stage.


Secondary Outcome Measures :
  1. To estimate the overall survival rates. [ Time Frame: Approximately 3 years ]
    Patients will be contacted every 3 months following treatment administration for up to three years to obtain survival data.

  2. To explore the effect of other covariates on overall survival [ Time Frame: 3 years ]
    To identify demographic, disease and treatment related effects on overall survival.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients > 18 years of age
  • Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or
  • Stage IV, American Joint Commission on Cancer)
  • Eastern Cooperative Oncology Group Performance Status of 0 to 2
  • Life expectancy > 3 months
  • At least 1 site of radiographically measurable disease by RECIST 1.1
  • Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:
  • Absolute neutrophil count > 1.0 x 10⁹/L
  • Platelet count > 50 x 10⁹/L
  • Hemoglobin > 8 g/dL
  • Serum creatinine < 2 x upper limit of normal
  • Total serum bilirubin < 3 x ULN
  • Serum aspartate transaminase or serum alanine transaminase < 3 x ULN, and < 4 x ULN if liver metastases are present
  • Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician
  • Pre-menopausal females and females < 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of the study drug
  • Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year
  • Before study entry, written informed consent must be obtained from the patient prior to performing any study related procedures

Exclusion Criteria:

  • Prior treatment with Vemurafenib or Dabrafenib
  • Known hypersensitivity to Metformin or any of its components
  • Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia
  • Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures
  • Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02143050


Contacts
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Contact: Stacy Baum, BSN 502-562-2280 msbaum02@louisville.edu
Contact: Karen Carter, BSN 502-562-3690 kmcart05@louisville.edu

Locations
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United States, Kentucky
James Graham Brown Cancer Center-Universityof Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Jason A Chesney, MD, PhD    502-562-3429    jason.chesney@louisville.edu   
Contact: Christina LaDuke    502-217-5205    christy.laduke@louisville.edu   
Sub-Investigator: Donald M Miller, MD, PhD         
Sub-Investigator: Kelly M McMasters, MD, PhD         
Sub-Investigator: Sucheta Telang, MD         
James Graham Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: Karen Carter, BSN    502-562-3690    kmcart05@louisville.edu   
Contact: Christina LaDuke, BS    502-217-5205    christi.laduke@louisville.edu   
Sponsors and Collaborators
James Graham Brown Cancer Center
University of Louisville
Investigators
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Principal Investigator: Jason A Chesney, MD, PhD James Graham Brown Cancer Center
More Information
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Responsible Party: James Graham Brown Cancer Center
ClinicalTrials.gov Identifier: NCT02143050    
Other Study ID Numbers: BCC-MEL-14-01
First Posted: May 20, 2014    Key Record Dates
Last Update Posted: November 23, 2016
Last Verified: November 2016
Keywords provided by James Graham Brown Cancer Center:
Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Metformin
 Trametinib
Dabrafenib
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action