A Phase I Study Of ZD1839 (Iressa TM), An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, In Children With Refractory Solid Tumors
N/A
21 Years
Both
Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
A Phase I Study Of ZD1839 (Iressa TM), An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, In Children With Refractory Solid Tumors
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by the Common Terminology Criteria (CTC) version 2.0
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Najat Daw
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01874
NCT ID:
NCT00040781
Start Date:
June 2002
Completion Date:
Related Keywords:
- Unspecified Childhood Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
