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Gefitinib in Treating Children With Refractory Solid Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00040781
Collaborator
(none)
45
Enrollment
1
Location
1
Arm

Study Details

Study Description

Brief Summary

Phase I trial to study the effectiveness of gefitinib in treating children who have refractory solid tumors. Gefitinib may stop the growth of cancer cells by blocking the enzymes necessary for tumor cell growth

Condition or Disease Intervention/Treatment Phase
  • Drug: gefitinib
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
 Phase 1

Detailed Description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of gefitinib in children with refractory solid tumors.

  2. Determine the dose-limiting toxicity of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. IV. Determine, preliminarily, the antitumor activity of this drug in these patients.

  3. Correlate the pharmacogenetic polymorphisms of this drug with pharmacokinetics and pharmacodynamics in these patients.

OUTLINE: This is a dose-escalation, multicenter study. If myelosuppression is found to be the dose-limiting toxicity, patients are stratified according to prior therapy (more than 2 multiagent chemotherapy regimens or radiotherapy to more than 20% of the bone marrow or stem cell transplantation with or without total body irradiation vs more than 2 single-agent phase I or phase II agents) and extent of disease (bone marrow involvement vs meeting none of the stratum I criteria).

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 3-45 patients will be accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study Of ZD1839 (Iressa TM), An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, In Children With Refractory Solid Tumors
Study Start Date :
Jun 1, 2002
Actual Primary Completion Date :
Oct 1, 2004

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (gefitinib)

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Drug: gefitinib
Given orally
Other Names:
  • Iressa
  • ZD 1839

    • Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies

    • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the Common Terminology Criteria (CTC) version 2.0 [28 days]

    2. DLT defined as hematologic and non-hematologic toxicities toxicities attributable to drug administration occurring during or immediately subsequent to the first course as assessed by CTC version 2.0 [28 days]

    3. Pharmacokinetics of gefitinib [At baseline, at 1, 2, 4, 6, 8, 12, and 24 hours after administration, at days 21 and 28, and at day 28 of subsequent courses]

    Secondary Outcome Measures

    1. Antitumor activity of gefitinib according to Response Evaluation Criteria in Solid Tumor (RECIST) [Up to 2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically confirmed solid tumor at original diagnosis

    • Refractory to conventional therapy and other therapies of higher priority according to the COG Phase I/II priority list or no conventional therapy exists

    • No primary CNS tumors or known metastases to the CNS

    • Performance status - Karnofsky 50-100% (over 10 years of age)

    • Performance status - Lansky 50-100% (10 years of age and under)

    • At least 8 weeks

    • Absolute neutrophil count at least 1,000/mm^3

    • Platelet count at least 50,000/mm^3 (transfusion independent)

    • Hemoglobin at least 8.0 g/dL (RBC transfusion allowed)

    • Bilirubin no greater than 1.5 times upper limit of normal (ULN)

    • ALT no greater than 3 times ULN

    • Albumin at least 2 g/dL

    • Creatinine normal for age

    • Glomerular filtration rate at least 70 mL/min

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • No uncontrolled infection

    • At least 6 months since prior allogeneic stem cell transplantation (SCT)

    • No evidence of active graft-versus-host disease

    • At least 1 week since prior biologic agents

    • At least 1 week since prior hematopoietic growth factors

    • Recovered from prior immunotherapy

    • At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered

    • No concurrent tamoxifen

    • At least 2 weeks since prior local palliative (small port) radiotherapy

    • At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis (6 weeks for radiotherapy to other substantial amount of bone marrow)

    • Recovered from prior radiotherapy

    • No concurrent drugs with known corneal toxicity (e.g., chlorpromazine, Amiodarone, or chloroquine)

    • No concurrent enzyme-activating anticonvulsants

    • No concurrent proton pump inhibitors or H-2 blockers within 4 hours of gefitinib administration

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Oncology Group Arcadia California United States 91006-3776

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Najat Daw, Children's Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00040781
    Other Study ID Numbers:
    • NCI-2012-01874
    • ADVL0016
    • U01CA097452
    • CDR0000069406
    • NCT00050739
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Jan 23, 2013
    Last Verified:
    Jan 1, 2013
    Additional relevant MeSH terms:
    Neoplasms
    Gefitinib

    Study Results

    No Results Posted as of Jan 23, 2013