Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

NCT02143050 | Withdrawn Phase 1 DMC

• 1 other identifier: BCC-MEL-14-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Melanoma

Keywords

Unresectable melanoma Stage IIIC and Stage IV BRAF V600E+

Outcome Measures

Primary Outcomes (2)

• 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.

  Duration of phase I portion, approxiately 6 months

• 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.

  6 years

Secondary Outcomes (2)

• To estimate the overall survival rates.

  Approximately 3 years

• To explore the effect of other covariates on overall survival

  3 years

Study Arms (1)

Dabrafenib, Trametinib and Metformin

EXPERIMENTAL

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; Drug: Trametinib; Drug: Metformin

Interventions

Dabrafenib DRUG

Also known as: Tafinlar

Dabrafenib, Trametinib and Metformin

Trametinib DRUG

Also known as: Mekinist

Dabrafenib, Trametinib and Metformin

Metformin DRUG

Also known as: Glucophage

Dabrafenib, Trametinib and Metformin

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Louisville: lead
• James Graham Brown Cancer Center: collaborator

Study Sites (2)

James Graham Brown Cancer Center-Universityof Louisville

Louisville, Kentucky, 40202, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; trametinib; Metformin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Jason A Chesney, MD, PhD

  James Graham Brown Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, James Graham Brown Cancer Center

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 20, 2014
• Study Start: September 1, 2014
• Primary Completion: November 17, 2017
• Study Completion: November 17, 2017
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

US (2)