Clinical trial NCT02143050: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: James Graham Brown Cancer Center
First posted: 2014-05-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Observation of two CTCAE drug related grade 4 toxicities in six patients.
timeFrame: Duration of phase I portion, approxiately 6 months
measure: Clinical Response Rate
timeFrame: 6 years
Secondary outcomes:
measure: To estimate the overall survival rates.
timeFrame: Approximately 3 years
measure: To explore the effect of other covariates on overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Louisville
country: United States
facility: James Graham Brown Cancer Center-Universityof Louisville
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
Study officials:
affiliation: James Graham Brown Cancer Center
name: Jason A Chesney, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: