RECRUITINGPhase 1 / Phase 2INTERVENTIONAL
A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients
A Phase I/II Trial of Vemurafenib and Metformin to Unresectable Stage IIIC and Stage IV BRAF.V600E+ Melanoma Patients
About This Trial
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.
Who May Be Eligible (Plain English)
Who May Qualify:
1. Male or female patients ≥ 18 years of age;
2. Patients with histological confirmed BRAFV600E melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer);
3. Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 2;
4. Life expectancy ≥ 3 months;
5. At least 1 site of radiographically measurable disease by RECIST 1.1
6. 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;
- blood count (hemoglobin) at least 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.
7. 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;
8. 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;
9. Before study entry, written willing to sign a consent form must be obtained from the patient prior to performing any study-related procedures.
Who Should NOT Join This Trial:
1. Prior treatment with Vemurafenib;
2. Known hypersensitivity to Metformin or any of its components;
3. Previous progression of melanoma while on Metformin;
...See full criteria on ClinicalTrials.gov
Always talk to your doctor about whether this trial is right for you.
Original Eligibility Criteria
View original clinical language
Inclusion Criteria:
1. Male or female patients ≥ 18 years of age;
2. Patients with histological confirmed BRAFV600E melanoma (Stage IIIC or Stage IV, American Joint Commission on Cancer);
3. Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 2;
4. Life expectancy ≥ 3 months;
5. At least 1 site of radiographically measurable disease by RECIST 1.1
6. 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.
7. 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;
8. 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;
9. Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.
Exclusion Criteria:
1. Prior treatment with Vemurafenib;
2. Known hypersensitivity to Metformin or any of its components;
3. Previous progression of melanoma while on Metformin;
4. 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;
5. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures;
6. Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study
Treatments Being Tested
DRUG
Vemurafenib
Vemurafenib (960 mg PO daily) in patients with unresectable BRAFV600E positive Stage IIIC and Stage IV melanoma
DRUG
Metformin
Metformin (500 mg PO BID x 2 weeks, then 850 mg PO BID)
Locations (1)
James Graham Brown Cancer Center-University of Louisville
Louisville, Kentucky, United States