Metformin in Children With Relapsed or Refractory Solid Tumors
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|ClinicalTrials.gov Identifier: NCT01528046|
Recruitment Status : Completed
First Posted : February 7, 2012
Last Update Posted : January 13, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors Primary Brain Tumors||Drug: Vincristine Drug: Irinotecan Drug: Temozolomide Drug: Metformin||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 24, 2012|
|Actual Primary Completion Date :||September 26, 2019|
|Actual Study Completion Date :||February 3, 2020|
Experimental: Metformin in Combination with VIT
Participants will receive metformin in combination with vincristine, irinotecan and temozolomide (VIT).
Vincristine (VCR) = 1.5 mg/m^2/day (maximum dose 2 mg), days 1 and 8, administered as intravenous (IV) bolus over 1-5 minutes
Irinotecan (IRN) = 50 mg/m^2/day, days 1-5, IV over 60 minutes
Temozolomide (TEM) = 50 mg/m^2/day by mouth (PO) Days 1-5
Metformin (MET) = dose as per dose escalation, divided twice a day (BID), PO continuously for the 21 day cycle.
- Maximum Tolerated Dose (MTD) [ Time Frame: Average of 3 Months ]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 ]To evaluate the antitumor activity of the addition of metformin to VIT.
- Pharmacokinetics [ Time Frame: Average of 3 Months ]To describe the pharmacokinetics of metformin in children with relapsed malignancies receiving VIT combination chemotherapy.
- Pharmacodynamics [ Time Frame: Average of 3 Months ]To define the pharmacodynamics of metformin.
- Metformin Concentrations [ Time Frame: Average of 3 Months ]To determine tissue and tumor metformin concentrations in patients undergoing resection.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||1 Year to 18 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 ≥ 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 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.
- 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.
- 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.
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): NCT01528046
|United States, Connecticut|
|Connecticut Children's Medical Center|
|Hartford, Connecticut, United States, 06106|
|United States, Delaware|
|Nemours/Alfred I. duPont Hospital for Children, Delaware|
|Wilmington, Delaware, United States, 19803|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32611|
|Nemours Children's Clinic|
|Jacksonville, Florida, United States, 32207|
|University of Miami Sylvester Comprehensive Cancer Center|
|Miami, Florida, United States, 33136|
|Johns Hopkins All Children's Hospital|
|Saint Petersburg, Florida, United States, 33701|
|Tampa General Hospital|
|Tampa, Florida, United States, 33606|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Kentucky|
|University of Kentucky|
|Lexington, Kentucky, United States, 40536|
|United States, Maryland|
|Johns Hopkins Sidney Kimmel Comprehensive Cancer Center|
|Baltimore, Maryland, United States, 21231|
|United States, New York|
|The Children's Hospital at Montefiore|
|Bronx, New York, United States, 10467|
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205|
|United States, Utah|
|Primary Children's Medical Center/Utah|
|Salt Lake City, Utah, United States, 84113|
|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|
|Responsible Party:||H. Lee Moffitt Cancer Center and Research Institute|
|Other Study ID Numbers:||
SP003 ( Other Grant/Funding Number: Pediatric Cancer Foundation )
|First Posted:||February 7, 2012 Key Record Dates|
|Last Update Posted:||January 13, 2023|
|Last Verified:||January 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
central nervous system (CNS)
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Antineoplastic Agents, Alkylating