Metformin 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.
Primary Brain Tumors
Drug: Vincristine sulfate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- 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.
- 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.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Metformin in Combination with VIT
All patients will receive 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:
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:Drug: Irinotecan
Irinotecan (IRN) = 50 mg/m^2/day, days 1-5, IV over 60 minutes
Other Names:Drug: Temozolomide
Temozolomide (TEM) = 100 mg/m^2/day PO Days 1-5
Other Names: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.
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.
|Contact: Kathleen Manningfirstname.lastname@example.org|
|Contact: Damon Reed, M.D.||email@example.com|
|United States, Delaware|
|Nemours/Alfred I. duPont Hospital for Children, Delaware||Recruiting|
|Wilmington, Delaware, United States, 19803|
|Contact: Debra J. Bertz 302-651-5757 firstname.lastname@example.org|
|Principal Investigator: Edward A. Kolb, M.D.|
|United States, Florida|
|University of Florida||Recruiting|
|Gainesville, Florida, United States, 32611|
|Contact: Heather Rogers 352-265-0027 email@example.com|
|Principal Investigator: Joanne Lagmay, M.D.|
|Sub-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.|
|Nemours Children's Clinic||Recruiting|
|Jacksonville, Florida, United States, 32207|
|Contact: Ingrid Ingram 904-697-3985 firstname.lastname@example.org|
|Principal Investigator: Scott Bradfield, M.D.|
|Sub-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.|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33124|
|Contact: Myriam Zayas 305-243-7846 MZayas2@med.miami.edu|
|Principal Investigator: John Goldberg, M.D.|
|Sub-Investigator: Cristina Fernandes, M.D.|
|Sub-Investigator: Joanna Davis, M.D.|
|Sub-Investigator: Antonello Podda, M.D.|
|Sub-Investigator: Andreansky Martin, M.D.|
|Sub-Investigator: Julio Barredo, M.D.|
|Sub-Investigator: Ofelia Alvarez, M.D.|
|All Children's Hospital||Recruiting|
|St. Petersburg, Florida, United States, 33701|
|Contact: Ashley Repp, RN 727-767-4784 Ashley.Repp@allkids.org|
|Contact: Frances Hamblin 727-767-2423 email@example.com|
|Principal Investigator: Damon Reed, M.D.|
|Sub-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.|
|United States, New York|
|The Children's Hospital at Montefiore||Recruiting|
|Bronx, New York, United States, 10467|
|Contact: Noam Zeffren 718-741-2356 firstname.lastname@example.org|
|Principal Investigator: Jonathan Gill, M.D.|
|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|