Metformin in Children With Relapsed or Refractory Solid Tumors

Conditions:Cancer, Brain Cancer
Therapuetic Areas:Oncology
Age Range:1 - 18
Start Date:April 25, 2012
End Date:December 2020
Contact:Tiffany Smith

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A Phase I Trial of Dose Escalation of Metformin in Combination With Vincristine, Irinotecan, and Temozolomide in Children With Relapsed or Refractory Solid Tumors

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.

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 16 years old, and Lansky ≥
50 for patients 1-16 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 ≥

- 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 patient's 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

- 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
We found this trial at
Lexington, Kentucky
859) 257-9000
Principal Investigator: Lars Wagner, M.D.
Phone: 859-323-6975
University of Kentucky The University of Kentucky is a public, land grant university dedicated to...
Lexington, KY
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Chapel Hill, North Carolina 27599
(919) 962-2211
Principal Investigator: Patrick Thompson, M.D.
Phone: 919-966-1178
University of North Carolina at Chapel Hill Carolina’s vibrant people and programs attest to the...
Chapel Hill, NC
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700 Childrens Drive
Columbus, Ohio 43205
(616) 722-2000
Principal Investigator: Bhuvana Setty, M.D.
Phone: 614-722-6570
Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
Columbus, OH
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Gainesville, Florida 32610
(352) 392-3261
Principal Investigator: Joanne Lagmay, M.D.
Phone: 352-265-0027
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
Gainesville, FL
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282 Washington St
Hartford, Connecticut 06106
(860) 545-9000
Principal Investigator: Michael Isakoff, M.D.
Phone: 860-545-9637
Connecticut Children's Medical Center Connecticut Children’s Medical Center is a nationally recognized, 187-bed not-for-profit children’s...
Hartford, CT
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807 Childrens Way
Jacksonville, Florida 32207
(904) 697-3600
Principal Investigator: Scott Bradfield, M.D.
Phone: 904-697-3985
Nemours Children's Clinic At Nemours Children’s Clinic, Jacksonville, we've treated every child as we would...
Jacksonville, FL
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1 Tampa General Cir
Tampa, Florida 33606
(813) 844-7000
Principal Investigator: Cameron Tebbi, M.D.
Phone: 813-844-7829
Tampa General Hospital In a diverse city known for its rich culture and beautiful beaches,...
Tampa, FL
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12902 USF Magnolia Dr
Tampa, Florida 33612
(888) 663-3488
Principal Investigator: Damon Reed, M.D.
Phone: 813-745-6250
H. Lee Moffitt Cancer Center & Research Institute Moffitt Cancer Center in Tampa, Florida, has...
Tampa, FL
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Baltimore, Maryland 21231
Principal Investigator: David Loeb, M.D.
Phone: 410-502-7247
Baltimore, MD
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Bronx, New York 10467
Principal Investigator: Jonathan Gill, M.D.
Phone: 718-741-2356
Bronx, NY
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1611 Northwest 12th Avenue
Miami, Florida 33124
Principal Investigator: John Goldberg, M.D.
Phone: 305-243-7846
Miami, FL
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Saint Petersburg, Florida 33701
Principal Investigator: Damon Reed, M.D.
Phone: 727-767-4784
Saint Petersburg, FL
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Salt Lake City, Utah 84113
Principal Investigator: Holly Spraker-Perlman, M.D.
Phone: 801-213-3909
Salt Lake City, UT
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Wilmington, Delaware 19803
Principal Investigator: Edward A. Kolb, M.D.
Phone: 302-651-5757
Wilmington, DE
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