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Trial record 1 of 1 for:    NCT01638676
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A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients

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ClinicalTrials.gov Identifier: NCT01638676
Recruitment Status : Recruiting
First Posted : July 12, 2012
Last Update Posted : November 23, 2016
Sponsor:
Collaborator:
University of Louisville
Information provided by (Responsible Party):
James Graham Brown Cancer Center

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Vemurafenib Drug: Metformin Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Vemurafenib and Metformin to Unresectable Stage IIIC and Stage IV BRAF.V600E+ Melanoma Patients
Study Start Date : July 2012
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: Vemurafenib and Metformin Drug: Vemurafenib
Vemurafenib (960 mg PO daily) in patients with unresectable BRAFV600E positive Stage IIIC and Stage IV melanoma
Other Name: Vemurafenib branded as Zelboraf

Drug: Metformin
Metformin (500 mg PO BID x 2 weeks, then 850 mg PO BID)
Other Name: Metformin hydrochloride branded as Glucophage




Primary Outcome Measures :
  1. Observation of CTCAE grade 4 or higher adverse events in six patients [ Time Frame: Duration of phase I portion, approximately six months ]
    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 :
  1. Overall Survival Follow up [ Time Frame: Every 12 weeks (+/- 7 days) after last drug dose, for up to 3 full years ]
    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.

  2. Number of adverse events [ Time Frame: Duration of study, estimated to be approximately 60 months ]
    Descriptive statistics of all AEs observed during the study period.

  3. type of adverse events [ Time Frame: Duration of study, estimated to be approximately 60 months ]
    Descriptive statistics of all AEs observed during the study period.

  4. Objective response rate (ORR)as measure of efficacy [ Time Frame: Duration of study (approximately 60 months) ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01638676


Locations
United States, Kentucky
James Graham Brown Cancer Center-University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Jason A Chesney, MD PhD    502-562-3429    jason.chesney@louisville.edu   
Contact: Sarah Lush, RN    502-540-1537    s.lush@louisville.edu   
Sponsors and Collaborators
James Graham Brown Cancer Center
University of Louisville
Investigators
Principal Investigator: Jason A Chesney, MD PhD James Graham Brown Cancer Center-U of Louisville

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Graham Brown Cancer Center
ClinicalTrials.gov Identifier: NCT01638676     History of Changes
Other Study ID Numbers: BCC-MEL-11-03
First Posted: July 12, 2012    Key Record Dates
Last Update Posted: November 23, 2016
Last Verified: November 2016

Keywords provided by James Graham Brown Cancer Center:
Unresectable melanoma
Stage IIIC and Stage IV BRAFV600E+ Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Metformin
Vemurafenib
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action