A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients

Overview[ - collapse ][ - ]

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.
ConditionMelanoma
InterventionDrug: Vemurafenib
Drug: Metformin
PhasePhase 1/Phase 2
SponsorJames Graham Brown Cancer Center
Responsible PartyJames Graham Brown Cancer Center
ClinicalTrials.gov IdentifierNCT01638676
First ReceivedJune 1, 2012
Last UpdatedNovember 13, 2013
Last verifiedNovember 2013

Tracking Information[ + expand ][ + ]

First Received DateJune 1, 2012
Last Updated DateNovember 13, 2013
Start DateJuly 2012
Estimated Primary Completion DateJune 2019
Current Primary Outcome MeasuresObservation of CTCAE grade 4 or higher adverse events in six patients [Time Frame: Duration of phase I portion, approximately six months] [Designated as safety issue: Yes]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.
Current Secondary Outcome Measures
  • Overall Survival Follow up [Time Frame: Every 12 weeks (+/- 7 days) after last drug dose, for up to 3 full years] [Designated as safety issue: No]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.
  • Number of adverse events [Time Frame: Duration of study, estimated to be approximately 60 months] [Designated as safety issue: Yes]Descriptive statistics of all AEs observed during the study period.
  • type of adverse events [Time Frame: Duration of study, estimated to be approximately 60 months] [Designated as safety issue: Yes]Descriptive statistics of all AEs observed during the study period.
  • Objective response rate (ORR)as measure of efficacy [Time Frame: Duration of study (approximately 60 months)] [Designated as safety issue: No]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

Descriptive Information[ + expand ][ + ]

Brief TitleA Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients
Official TitleA Phase I/II Trial of Vemurafenib and Metformin to Unresectable Stage IIIC and Stage IV BRAF.V600E+ Melanoma Patients
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.
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.
Study TypeInterventional
Study PhasePhase 1/Phase 2
Study DesignEndpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionMelanoma
InterventionDrug: Vemurafenib
Vemurafenib (960 mg PO daily) in patients with unresectable BRAFV600E positive Stage IIIC and Stage IV melanoma
Other Names:
Vemurafenib branded as ZelborafDrug: Metformin
Metformin (500 mg PO BID x 2 weeks, then 850 mg PO BID)
Other Names:
Metformin hydrochloride branded as Glucophage
Study Arm (s)Experimental: Vemurafenib and Metformin

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment55
Estimated Completion DateJune 2019
Estimated Primary Completion DateJune 2018
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01638676
Other Study ID NumbersBCC-MEL-11-03
Has Data Monitoring CommitteeYes
Information Provided ByJames Graham Brown Cancer Center
Study SponsorJames Graham Brown Cancer Center
CollaboratorsUniversity of Louisville
Investigators Principal Investigator: Jason A Chesney, MD PhD James Graham Brown Cancer Center-U of Louisville
Verification DateNovember 2013

Locations[ + expand ][ + ]

James Graham Brown Cancer Center-University of Louisville
Louisville, Kentucky, United States, 40202
Contact: Jason A Chesney, MD PhD | 502-562-3429 | jason.chesney@louisville.edu
Recruiting