Description:
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.
Title
- Brief Title: A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients
- Official Title: A Phase I/II Trial of Vemurafenib and Metformin to Unresectable Stage IIIC and Stage IV BRAF.V600E+ Melanoma Patients
Clinical Trial IDs
- ORG STUDY ID:
BCC-MEL-11-03
- NCT ID:
NCT01638676
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Vemurafenib | Vemurafenib branded as Zelboraf | Vemurafenib and Metformin |
Metformin | Metformin hydrochloride branded as Glucophage | Vemurafenib and Metformin |
Purpose
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.
Detailed Description
This is a Phase I/II study. Phase I will be evaluating the safety of the FDA-approved
Vemurafenib (960 mg orally, daily) in combination with Metformin (500 mg orally, twice daily
for 2 weeks, then 850 mg orally,twice daily) in patients with unresectable Stage IIIC and
Stage IV melanoma. Phase II will evaluate the clinical activity of the combined
Vemurafenib/Metformin regimen. The safety profile of this combined Vemurafenib/Metformin
regimen will be monitored during both phases. The treatment period consists of 28-day cycles
until progression or unacceptable toxicity occurs.
Trial Arms
Name | Type | Description | Interventions |
---|
Vemurafenib and Metformin | Experimental | | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Observation of CTCAE grade 4 or higher adverse events in six patients |
Time Frame: | Duration of phase I portion, approximately six months |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Overall Survival Follow up |
Time Frame: | Every 12 weeks (+/- 7 days) after last drug dose, for up to 3 full years |
Safety Issue: | |
Description: | Patients will be followed for up to three years following the last treatment administration. The Investigator or designees will make every possible attempt at least every 12 weeks (±7 days), for up to three years after the last treatment to contact the patient or family to obtain the survival information of the patient and, if applicable, the start date of additional anticancer treatment. |
Measure: | Number of adverse events |
Time Frame: | Duration of study, estimated to be approximately 60 months |
Safety Issue: | |
Description: | Descriptive statistics of all AEs observed during the study period. |
Measure: | type of adverse events |
Time Frame: | Duration of study, estimated to be approximately 60 months |
Safety Issue: | |
Description: | Descriptive statistics of all AEs observed during the study period. |
Measure: | Objective response rate (ORR)as measure of efficacy |
Time Frame: | Duration of study (approximately 60 months) |
Safety Issue: | |
Description: | Efficacy estimated as the objective response rate (ORR), which is the sum of Partial Responses (PR) and Complete Responses (CR) as determined by RECIST 1.1 |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | James Graham Brown Cancer Center |
Trial Keywords
- Unresectable melanoma
- Stage IIIC and Stage IV BRAFV600E+ Melanoma
Last Updated
November 23, 2016