Metformin in Children With Relapsed or Refractory Solid Tumors
Information source: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Solid Tumors; Primary Brain Tumors
Intervention: Vincristine sulfate (Drug); Irinotecan (Drug); Temozolomide (Drug); Metformin (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: H. Lee Moffitt Cancer Center and Research Institute Official(s) and/or principal investigator(s): Jonathan Gill, M.D., Study Chair, Affiliation: The Children's Hospital at Montefiore, Pediatric Cancer Foundation, Sunshine Project Damon Reed, M.D., Principal Investigator, Affiliation: H. Lee Moffitt Cancer Center and Research Institute
Overall contact: Kathleen Manning, Phone: 813-745-7412, Email: kathleen.manning@moffitt.org
Summary
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.
Clinical Details
Official title: A Phase I Trial of Dose Escalation of Metformin in Combination With Vincristine, Irinotecan, and Temozolomide in Children With Relapsed or Refractory Solid Tumors
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum Tolerated Dose (MTD)
Secondary outcome: Number of Participants with Antitumor ActivityPharmacokinetics Pharmacodynamics Metformin Concentrations
Detailed description:
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.
Eligibility
Minimum age: 1 Year.
Maximum age: 18 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Kathleen Manning, Phone: 813-745-7412, Email: kathleen.manning@moffitt.org
Connecticut Children's Medical Center, Hartford, Connecticut 06106, United States; Recruiting Robin Arens, Phone: 860-545-9637, Email: Rarens@ccmckids.org Michael Isakoff, M.D., Principal Investigator Donna Boruchov, M.D., Sub-Investigator Kerry Moss, M.D., Sub-Investigator Andrea Orsey, M.D., Sub-Investigator Nehal Parikh, M.D., Sub-Investigator Arnold Altman, M.D., Sub-Investigator
Nemours/Alfred I. duPont Hospital for Children, Delaware, Wilmington, Delaware 19803, United States; Recruiting Debra J. Bertz, Phone: 302-651-5757, Email: debra.bertz@nemours.org Edward A. Kolb, M.D., Principal Investigator Andrew Walter, M.D., Sub-Investigator Jonathan Powell, M.D., Sub-Investigator Emi Caywood, M.D., Sub-Investigator Robin Miller, M.D., Sub-Investigator Gregory Griffin, M.D., Sub-Investigator
University of Florida, Gainesville, Florida 32611, United States; Recruiting Heather Rogers, Phone: 352-265-0027, Email: heatherrogers@ufl.edu Joanne Lagmay, M.D., Principal Investigator Tung Wynn, M.D., Sub-Investigator William Slayton, M.D., Sub-Investigator Lamis Eldjerou, M.D., Sub-Investigator John Fort, M.D., Sub-Investigator Levette Dunbar, M.D., Sub-Investigator
Nemours Children's Clinic, Jacksonville, Florida 32207, United States; Recruiting Ingrid Ingram, Phone: 904-697-3985, Email: iingram@nemours.org Scott Bradfield, M.D., Principal Investigator Eric Sandler, M.D., Sub-Investigator Michael Joyce, M.D., Sub-Investigator Cynthia Gauger, M.D., Sub-Investigator Manisha Bansal, M.D., Sub-Investigator Paul Pitel, M.D., Sub-Investigator
University of Miami, Miami, Florida 33124, United States; Recruiting Myriam Zayas, Phone: 305-243-7846, Email: MZayas2@med.miami.edu John Goldberg, M.D., Principal Investigator Cristina Fernandes, M.D., Sub-Investigator Joanna Davis, M.D., Sub-Investigator Antonello Podda, M.D., Sub-Investigator Martin Andreansky, M.D., Sub-Investigator Julio Barredo, M.D., Sub-Investigator Ofelia Alvarez, M.D., Sub-Investigator
All Children's Hospital, St. Petersburg, Florida 33701, United States; Recruiting Ashley Repp, RN, Phone: 727-767-4784, Email: Ashley.Repp@allkids.org Frances Hamblin, Phone: 727-767-2423, Email: frances.hamblin@allkids.org Damon Reed, M.D., Principal Investigator Irmel Ayala, M.D., Sub-Investigator Gregory Hale, M.D., Sub-Investigator Nanette Grana, M.D., Sub-Investigator Stacie Stapleton, M.D., Sub-Investigator Kelly Sawczyn, M.D., Sub-Investigator Jennifer Mayer, M.D., Sub-Investigator Jody Kerr, M.D., Sub-Investigator
Tampa General Hospital, Tampa, Florida 33606, United States; Recruiting Denise Fife, Phone: 813-844-7829, Email: dafife@tgh.org Cameron Tebbi, M.D., Principal Investigator
The Children's Hospital at Montefiore, Bronx, New York 10467, United States; Recruiting Noam Zeffren, Phone: 718-741-2356, Email: nzeffren@montefiore.org Jonathan Gill, M.D., Principal Investigator
Primary Children's Medical Center/Utah, Salt Lake City, Utah 84113, United States; Recruiting Melissa Bolton, Phone: 801-213-3909, Email: melissa.bolton@hsc.utah.edu Holly Spraker-Perlman, M.D., Principal Investigator Richard Lemons, M.D., Ph.D., Sub-Investigator Jennifer Wright, M.D., Sub-Investigator
Additional Information
Moffitt Cancer Center Clinical Trials website
Starting date: September 2012
Last updated: July 22, 2015
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