Metformin in Children With Relapsed or Refractory Solid Tumors

NCT01528046 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-16962SP003
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Solid Tumors; Primary Brain Tumors

Keywords

central nervous system (CNS); malignancy; relapsed; refractory; pediatric; recurrent

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose (MTD) of metformin when given in conjunction with VIT in children with refractory and relapsed solid tumors.

  Average of 3 Months

Secondary Outcomes (4)

• Number of Participants with Antitumor Activity

  Average of 3 Months

• Pharmacokinetics

  Average of 3 Months

• Pharmacodynamics

  Average of 3 Months

• Metformin Concentrations

  Average of 3 Months

Study Arms (1)

Metformin in Combination with VIT

EXPERIMENTAL

Participants will receive metformin in combination with vincristine, irinotecan and temozolomide (VIT).

Drug: Vincristine; Drug: Irinotecan; Drug: Temozolomide; Drug: Metformin

Interventions

Vincristine DRUG

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

Also known as: VCR, Oncovin, NSC #067574, Vincristine sulfate

Metformin in Combination with VIT

Irinotecan DRUG

Irinotecan (IRN) = 50 mg/m\^2/day, days 1-5, IV over 60 minutes

Also known as: CPT-11, Camptothecin-11, Camptosar ®, NSC#616348, IRN

Metformin in Combination with VIT

Temozolomide DRUG

Temozolomide (TEM) = 50 mg/m\^2/day by mouth (PO) Days 1-5

Also known as: Temodar™, NSC #362856, TEM

Metformin in Combination with VIT

Metformin DRUG

Metformin (MET) = dose as per dose escalation, divided twice a day (BID), PO continuously for the 21 day cycle.

Also known as: Glucophage ®, MET

Metformin in Combination with VIT

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Pediatric Cancer Foundation: collaborator

Study Sites (14)

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Nemours/Alfred I. duPont Hospital for Children, Delaware

Wilmington, Delaware, 19803, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

The Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Primary Children's Medical Center/Utah

Salt Lake City, Utah, 84113, United States

Location

Related Publications (1)

• Metts JL, Trucco M, Weiser DA, Thompson P, Sandler E, Smith T, Crimella J, Sansil S, Thapa R, Fridley BL, Llosa N, Badgett T, Gorlick R, Reed D, Gill J. A phase I trial of metformin in combination with vincristine, irinotecan, and temozolomide in children with relapsed or refractory solid and central nervous system tumors: A report from the national pediatric cancer foundation. Cancer Med. 2023 Feb;12(4):4270-4281. doi: 10.1002/cam4.5297. Epub 2022 Sep 23.

  PMID: 36151773 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Neoplasms; Recurrence

Interventions

Vincristine; Irinotecan; Temozolomide; Metformin

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Camptothecin; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Biguanides; Guanidines; Amidines

Study Officials

• Jonathan Gill, M.D.

  The Children's Hospital at Montefiore, Pediatric Cancer Foundation, Sunshine Project

  STUDY CHAIR

• Damon Reed, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2012
• First Posted: February 7, 2012
• Study Start: September 24, 2012
• Primary Completion: September 26, 2019
• Study Completion: February 3, 2020
• Last Updated: January 13, 2023

Record last verified: 2023-01

Locations

US (14)