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Trial record 1 of 1 for:    Metformin in Combination with Vincristine, Irinotecan, and Temozolomide
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Metformin in Children With Relapsed or Refractory Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by H. Lee Moffitt Cancer Center and Research Institute
Pediatric Cancer Foundation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute Identifier:
First received: February 3, 2012
Last updated: September 10, 2014
Last verified: September 2014

February 3, 2012
September 10, 2014
September 2012
April 2015   (final data collection date for primary outcome measure)
Maximum Tolerated Dose (MTD) [ Time Frame: Average of 3 Months ] [ Designated as safety issue: Yes ]
To determine the maximum tolerated dose (MTD) of metformin when given in conjunction with VIT in children with refractory and relapsed solid tumors.
Same as current
Complete list of historical versions of study NCT01528046 on Archive Site
  • Number of Participants with Antitumor Activity [ Time Frame: Average of 3 Months ] [ Designated as safety issue: No ]
    To evaluate the antitumor activity of the addition of metformin to VIT.
  • Pharmacokinetics [ Time Frame: Average of 3 Months ] [ Designated as safety issue: No ]
    To describe the pharmacokinetics of metformin in children with relapsed malignancies receiving VIT combination chemotherapy.
  • Pharmacodynamics [ Time Frame: Average of 3 Months ] [ Designated as safety issue: No ]
    To define the pharmacodynamics of metformin.
  • Metformin Concentrations [ Time Frame: Average of 3 Months ] [ Designated as safety issue: No ]
    To determine tissue and tumor metformin concentrations in patients undergoing resection.
Same as current
Not Provided
Not Provided
Metformin in Children With Relapsed or Refractory Solid Tumors
A Phase I Trial of Dose Escalation of Metformin in Combination With Vincristine, Irinotecan, and Temozolomide in Children With Relapsed or Refractory Solid Tumors

H. Lee Moffitt Cancer Center and Research Institute will be the Sunshine Project Coordinator, but will not be recruiting locally.

The purpose of this study is to evaluate the tolerability and safety of escalating doses of metformin on a backbone of vincristine, irinotecan and temozolomide (VIT) in children with recurrent and refractory solid tumors.

Metformin is an oral anti-diabetes medication that activates AMP-activated protein kinase (AMPK). Recent data from in vitro and in vivo experiments, as well as epidemiologic retrospective analyses, suggest that metformin has anti-cancer activity. Vincristine, irinotecan, and temozolomide (VIT) is a combination of chemotherapeutic agents that have different mechanisms of action as well as disparate side effect profiles. Two recent phase 1 trials have demonstrated that this regimen is safe and well-tolerated in children with relapsed and refractory solid tumors.

Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Solid Tumors
  • Primary Brain Tumors
  • Drug: Vincristine sulfate
    Vincristine (VCR) = 1.5 mg/m^2/day (maximum dose 2 mg), days 1 and 8, administered as IV bolus over 1-5 minutes
    Other Names:
    • VCR
    • Oncovin
    • NSC #067574
  • Drug: Irinotecan
    Irinotecan (IRN) = 50 mg/m^2/day, days 1-5, IV over 60 minutes
    Other Names:
    • CPT-11
    • Camptothecin-11
    • Camptosar ®
    • NSC#616348
    • IRN
  • Drug: Temozolomide
    Temozolomide (TEM) = 100 mg/m^2/day PO Days 1-5
    Other Names:
    • Temodar™
    • NSC #362856
    • TEM
  • Drug: Metformin
    Metformin (MET) = dose as per dose escalation, divided BID, PO continuously Metformin will only be started after the completion of first cycle, in patients who have demonstrated no significant bone marrow suppression with VIT only.
    Other Names:
    • Glucophage ®
    • MET
Experimental: Metformin in Combination with VIT

All patients will receive vincristine, irinotecan and temozolomide (VIT) only for their initial cycle of protocol treatment.

All patients who have no significant bone marrow suppression (hematologic parameters recovered by Day 21, meeting eligibility criteria to proceed to next cycle) will proceed with metformin as per dose escalation with the second and all subsequent cycles.

For patients with bone marrow suppression not recovered by Day 21:

  • Dose modification as per protocol
  • Second cycle with VIT only, to validate that dose modification has resolved the bone marrow suppression.

    • Patients who tolerate dose modification with their second cycle will receive metformin with their subsequent cycles as per dose escalation stratum.
    • Patients who had dose modification and do not recover by Day 21 to meet eligibility criteria will be removed from study prior to receiving metformin and will be considered unevaluable.
  • Drug: Vincristine sulfate
  • Drug: Irinotecan
  • Drug: Temozolomide
  • Drug: Metformin
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
April 2015
April 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age: Patients must be > 1 year of age and ≤ 18 years of age at time of initiation of protocol therapy.
  • Diagnosis: Patients have a histologically or radiographically confirmed relapsed or refractory solid tumor or primary central nervous system (CNS) malignancy.
  • Disease Status: Patients must have radiographically measurable disease.
  • Therapeutic Options: Patients must have relapsed or refractory cancers for which there is no known curative option or other available therapy proven to prolong survival with an acceptable quality of life.
  • Performance Level: Karnofsky ≥ 50% for patients older than 10 years old, and Lansky ≥ 50 for patients ≤ 10 years old.
  • Prior Therapy: Patients may have received prior therapy including vincristine, irinotecan, or temozolomide. Patients may not have previously been treated with combination therapy of irinotecan and temozolomide.
  • Patients must be fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

    • Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of starting protocol therapy, or a minimum of six weeks must have elapsed since prior nitrosurea chemotherapy.
    • Hematopoietic growth factor: At least 7 days must have elapsed since the last administration of filgrastim, or 14 days since administration of pegfilgrastim.
    • Biologic (anti-neoplastic agent): At least 7 must have elapsed since the last administration of any biologic agent.
    • Radiation therapy (XRT): At least 14 days since the last dose of local palliative radiation therapy. Greater than 6 months must have elapsed since the last day of treatment if given total body irradiation, craniospinal irradiation.
    • Autologous or Allogenic Stem Cell Transplant: Complete resolution of graft versus host disease and no current need for immunosuppressive medication. Greater than 3 months must have elapsed since engraftment and no longer requiring transfusion of platelets or injection of colony stimulating factors.
  • Organ Function Requirements

    • Bone Marrow Function: Peripheral absolute neutrophil count (ANC) ≥ 1000/μL; Platelet count ≥ 100,000/μL (no platelet transfusion within 7 days prior to obtaining laboratory result); Hemoglobin ≥ 8.0 gm/dL
    • Adequate Renal Function: Creatinine clearance or glomerular filtration rate ≥ 70ml/min/1.73m^2
    • Adequate Liver Function: Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age; alanine transaminase (ALT) ≤ 5x ULN; Serum albumin ≥ 2gm/dL
  • Informed Consent: All patients ≥ 18 years of age must sign a written informed consent. For patients < 18 years old, the patients' parents or legal guardians must sign a written informed consent, unless the patient is an emancipated minor. Childhood Assent, when age appropriate as per institutional guidelines, should be signed by the participating patient.

Exclusion Criteria:

  • Significant organ dysfunction, not meeting inclusion criteria.
  • Pregnancy or Breast-Feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
  • Concomitant Medications:

    • Growth factor: Growth factors that support platelet or white cell number of function must not have been administered within the past 7 days.
    • Steroids: Patients with CNS tumors who have not been on a stable or decreasing dose of dexamethasone for the past 7 days.
    • Investigational Drugs: Patients who are currently receiving another investigational drug.
    • Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents.
    • Medication Allergy: Allergy or intolerance to agents on this protocol: vincristine, irinotecan, temozolomide, or metformin; Allergy to cephalosporins.
    • Infection: Patients who have uncontrolled infection, positive blood cultures within the past 48 hours, or receiving treatment for Clostridium difficile infection.
1 Year to 18 Years
Contact: Kathleen Manning 813-745-7412
Contact: Damon Reed, M.D. 813-745-2297
United States
MCC-16962, SP003
H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
Pediatric Cancer Foundation
Study Chair: Jonathan Gill, M.D. The Children's Hospital at Montefiore, Pediatric Cancer Foundation, Sunshine Project
Principal Investigator: Damon Reed, M.D. H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP