Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Gefitinib in Treating Children With Refractory Solid Tumors

Basic Trial Information

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.
3. Determine the pharmacokinetics of this drug in these patients.
4. Determine, preliminarily, the antitumor activity of this drug in these patients.
5. Correlate the pharmacogenetic polymorphisms of this drug with pharmacokinetics and pharmacodynamics in these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy:

• 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

Chemotherapy:

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

Endocrine therapy:

• No concurrent tamoxifen

Radiotherapy:

• 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

Surgery:

• Not specified

Other:

• No concurrent drugs with known corneal toxicity (e.g., chlorpromazine, amiodarone, or chloroquine)
• No concurrent enzyme-activating anticonvulsants
• No concurrent proton pump inhibitors or H₂ blockers within 4 hours of gefitinib administration

Patient Characteristics:

Age:

• Under 22

Performance status:

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

  OR

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

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 50,000/mm³ (transfusion independent)
• Hemoglobin at least 8.0 g/dL (RBC transfusion allowed)

Hepatic:

• 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

Renal:

• Creatinine normal for age

  OR

• Glomerular filtration rate at least 70 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection

Expected Enrollment

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

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.

Jimeno A, Daw NC, Amador ML, et al.: Analysis of biologic surrogate markers from a Children's Oncology Group Phase I trial of gefitinib in pediatric patients with solid tumors. Pediatr Blood Cancer 49 (3): 352-7, 2007.[PUBMED Abstract]

Daw NC, Furman WL, Stewart CF, et al.: Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol 23 (25): 6172-80, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Najat Daw, MD, Protocol chair		Ph: 901-495-2573 Email: najat.daw@stjude.org

Registry Information
Official Title		A Phase I Study Of ZD1839 (Iressa), An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, In Children With Refractory Solid Tumors
Trial Start Date		2002-06-03
Registered in ClinicalTrials.gov		NCT00040781
Date Submitted to PDQ		2002-05-02
Information Last Verified		2005-02-04
NCI Grant/Contract Number		U10-CA13539

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