DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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 Activity

Pharmacokinetics

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

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017