Gefitinib in Treating Children With Refractory Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Childhood Solid Tumor, Protocol Specific

Treatments

Drug: gefitinib

Other: pharmacological study

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00040781

NCI-2012-01874

CDR0000069406 (Registry Identifier)

U01CA097452 (U.S. NIH Grant/Contract)

ADVL0016

Details and patient eligibility

About

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

Full 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.

Enrollment

45 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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