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Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

Primary Purpose

Melanoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dabrafenib
Trametinib
Metformin
Sponsored by
University of Louisville
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • James Graham Brown Cancer Center-Universityof LouisvilleRecruiting
  • James Graham Brown Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dabrafenib, Trametinib and Metformin

Arm Description

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.

Outcomes

Primary Outcome Measures

Observation of two CTCAE drug related grade 4 toxicities in six patients.
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.
Clinical Response Rate
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

To estimate the overall survival rates.
Patients will be contacted every 3 months following treatment administration for up to three years to obtain survival data.
To explore the effect of other covariates on overall survival
To identify demographic, disease and treatment related effects on overall survival.

Full Information

First Posted
May 13, 2014
Last Updated
October 22, 2021
Sponsor
University of Louisville
Collaborators
James Graham Brown Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT02143050
Brief Title
Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients
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 Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 2014 (undefined)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Louisville
Collaborators
James Graham Brown Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dabrafenib, Trametinib and Metformin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dabrafenib
Other Intervention Name(s)
Tafinlar
Intervention Type
Drug
Intervention Name(s)
Trametinib
Other Intervention Name(s)
Mekinist
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Primary Outcome Measure Information:
Title
Observation of two CTCAE drug related grade 4 toxicities in six patients.
Description
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.
Time Frame
Duration of phase I portion, approxiately 6 months
Title
Clinical Response Rate
Description
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.
Time Frame
6 years
Secondary Outcome Measure Information:
Title
To estimate the overall survival rates.
Description
Patients will be contacted every 3 months following treatment administration for up to three years to obtain survival data.
Time Frame
Approximately 3 years
Title
To explore the effect of other covariates on overall survival
Description
To identify demographic, disease and treatment related effects on overall survival.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stacy Baum, BSN
Phone
502-562-2280
Email
msbaum02@louisville.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Karen Carter, BSN
Phone
502-562-3690
Email
kmcart05@louisville.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason A Chesney, MD, PhD
Organizational Affiliation
James Graham Brown Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
James Graham Brown Cancer Center-Universityof Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason A Chesney, MD, PhD
Phone
502-562-3429
Email
jason.chesney@louisville.edu
First Name & Middle Initial & Last Name & Degree
Christina LaDuke
Phone
502-217-5205
Email
christy.laduke@louisville.edu
First Name & Middle Initial & Last Name & Degree
Donald M Miller, MD, PhD
First Name & Middle Initial & Last Name & Degree
Kelly M McMasters, MD, PhD
First Name & Middle Initial & Last Name & Degree
Sucheta Telang, MD
Facility Name
James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Carter, BSN
Phone
502-562-3690
Email
kmcart05@louisville.edu
First Name & Middle Initial & Last Name & Degree
Christina LaDuke, BS
Phone
502-217-5205
Email
christi.laduke@louisville.edu

12. IPD Sharing Statement

Learn more about this trial

Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

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