Tarceva/Rapamycin for Children With Low-grade Gliomas With or Without Neurofibromatosis Type 1 (NF1)

Phase 1 Study of Tarceva and Rapamycin For Recurrent Low-Grad Gliomas in Children With or Without Neurofibromatosis Type 1 (NF1)

This study will evaluate the feasibility of combining two drugs, Tarceva (an anti-EGFR agent), and Rapamycin (an mTOR inhibitor), in children with progressive low-grade gliomas who have failed initial conventional treatment. In addition to evaluating the toxicity of this drug regimen, the potential efficacy of the regimen will be assessed.

Study Overview

• Status: Completed
• Conditions: Low-grade Gliomas
• Intervention / Treatment: Drug: Tarceva and Rapamycin

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children less than 21 years of age, with or without neurofibromatosis, with recurrent low-grade gliomas.
• patients with or without NF1 must have failed some form of conventional therapy, radiotherapy, or chemotherapy (carboplatin/vincristine) to be eligible, including those treated wtih initial surgery. Patients do not have to have received radiotherapy to be eligible.
• children with all types of histologically proven low-grade gliomas will be eligible; re-operation at the time of recurrence is not mandatory for entry on study.
• patients with intrinsic brain lesions, believed neuroradiographically consistent with a low-grade glial tumor, with neurofibromatosis type 1 can be treated without histological confirmation.
• patients without neurofibromatosis type 1 must have histological confirmation of a low-grade glial tumor prior to entry on study.
• patients must have a Karnofsky score of greater than or equal to 50% for children greater than 10 years of age, or a Lansky score of greater than or equal to 50% for patients less than 10 years of age.
• patients who are unable to walk because of paralysis, but who are able to use a wheelchair, will be considered ambulatory for purposes of assessing performance score.
• patients must have a life expectancy of at least 12 weeks.
• patients must be able to swallow medication in tablet form.
• patients must have adequate organ function, including: peripheral ANC of greater than 1,000/microliters; a platelet count of greater than 100,000/microliters; hemoglobin of greater than 8 gms,dl (pRBC transfusions of allowed to maintain hemoglobin > 8 g/dl)
• patients must have adequate renal function, which is defined as a normal serum creatinine for age
• patients must have adequate liver function, as defined as a total bilirubin or less than 1.5 times the upper limit of normal for age, and an SGPT (ALT) of less than 2.5 times the upper limit of normal for age
• patients must have had a MR scan within 3 weeks of starting treatment
• all patients, and/or their parents or legal guardian, must sign a recent informed consent
• all institutional, FDA, and NCI requirements for human study must be met.

Exclusion Criteria:

• patients must not have any other active tumors.
• pregnancy or breast feeding is an exclusion criteria, as the potential mutagenicity and cytotoxicity of these drugs in developing fetuses are unknown. A pregnancy test must be obtained in females who are postmenarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• patients with uncontrolled infection are excluded.
• patients who have previously received Tarceva or Rapamycin are excluded.
• patients on antiepileptics and/or corticosteroids are allowed on study as long as they have been on a stable or weaning dose for 7 days prior to study initiation (defined as first day of treatment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Participants will remain on the trial for one year if benefiting from drug as demonstrated by radiographic evaluation and clinical evaluation.	one year

Collaborators and Investigators

• Sponsor: Roger Packer
• Collaborators: Children's National Research Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: May 13, 2009
• First Submitted That Met QC Criteria: May 13, 2009
• First Posted (Estimate): May 14, 2009

Study Record Updates

• Last Update Posted (Estimate): September 16, 2014
• Last Update Submitted That Met QC Criteria: September 12, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Glioma; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Erlotinib Hydrochloride; Sirolimus
• Other Study ID Numbers: 4104