A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients
1 other identifier
interventional
55
1 country
1
Brief Summary
The main purpose of this study is to evaluate the safety of Vemurafenib in combination with Metformin in melanoma patients. The phase II part of the study will also evaluate the clinical activity of the combined regiment. Based on pre-clinical studies and a phase I trial, the investigators hypothesize that the combination of an FDA-approved non-toxic dose of oral Metformin with Vemurafenib will yield little toxicity and improve clinical outcomes in terms of objective response rates and survival in metastatic melanoma patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2012
Longer than P75 for phase_1
1 active site
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
First Submitted
Initial submission to the registry
June 1, 2012
CompletedStudy Start
First participant enrolled
July 1, 2012
CompletedFirst Posted
Study publicly available on registry
July 12, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
ExpectedOctober 29, 2021
October 1, 2021
12.9 years
June 1, 2012
October 22, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Observation of CTCAE grade 4 or higher adverse events in six patients
In the phase I portion, six patients will be enrolled and observed for CTCAE grade 4 or higher events. If three or more grade 4 or higher adverse events are observed among the six patients, the study will be halted.
Duration of phase I portion, approximately six months
Secondary Outcomes (4)
Overall Survival Follow up
Every 12 weeks (+/- 7 days) after last drug dose, for up to 3 full years
Number of adverse events
Duration of study, estimated to be approximately 60 months
type of adverse events
Duration of study, estimated to be approximately 60 months
Objective response rate (ORR)as measure of efficacy
Duration of study (approximately 60 months)
Study Arms (1)
Vemurafenib and Metformin
EXPERIMENTALInterventions
Vemurafenib (960 mg PO daily) in patients with unresectable BRAFV600E positive Stage IIIC and Stage IV melanoma
Metformin (500 mg PO BID x 2 weeks, then 850 mg PO BID)
Eligibility Criteria
You may qualify if:
- Male or female patients ≥ 18 years of age;
- Patients with histological confirmed BRAFV600E melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer);
- Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) 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 (ANC) ≥ 1.0 x 109/L;
- Platelet count ≥ 50 x 109/L;
- Hemoglobin ≥ 8 g/dL;
- Serum creatinine ≤ 2 x upper limit of normal (ULN)
- Total serum bilirubin ≤ 3 x ULN;
- Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT) ≤ 3x 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 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.
You may not qualify if:
- Prior treatment with Vemurafenib;
- Known hypersensitivity to Metformin or any of its components;
- Previous progression of melanoma while on Metformin;
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Louisvillelead
- James Graham Brown Cancer Centercollaborator
Study Sites (1)
James Graham Brown Cancer Center-University of Louisville
Louisville, Kentucky, 40202, United States
Related Publications (1)
Cerezo M, Tomic T, Ballotti R, Rocchi S. Is it time to test biguanide metformin in the treatment of melanoma? Pigment Cell Melanoma Res. 2015 Jan;28(1):8-20. doi: 10.1111/pcmr.12267. Epub 2014 Jun 26.
PMID: 24862830DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jason A Chesney, MD PhD
James Graham Brown Cancer Center-U of Louisville
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
June 1, 2012
First Posted
July 12, 2012
Study Start
July 1, 2012
Primary Completion
June 1, 2025
Study Completion (Estimated)
June 1, 2027
Last Updated
October 29, 2021
Record last verified: 2021-10