Gefitinib in Treating Children With Refractory Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00040781
First received: July 8, 2002
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: gefitinib
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the Common Terminology Criteria (CTC) version 2.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of gefitinib [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor activity of gefitinib according to Response Evaluation Criteria in Solid Tumor (RECIST) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: June 2002
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

II. 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.

V. 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00040781

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Najat Daw Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00040781     History of Changes
Obsolete Identifiers: NCT00050739
Other Study ID Numbers: NCI-2012-01874, ADVL0016, U01CA097452, CDR0000069406
Study First Received: July 8, 2002
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Gefitinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014