A Phase I Study of ZD1839 (Iressa) in Combination With Irinotecan (Camptosar or CPT-11) and Vincristine in Pediatric Patients With Refractory Solid Tumors
N/A
21 Years
Both
Solid Tumors
Trial Information
A Phase I Study of ZD1839 (Iressa) in Combination With Irinotecan (Camptosar or CPT-11) and Vincristine in Pediatric Patients With Refractory Solid Tumors
Objectives of this study are:
- To determine the dose-limiting toxicities (DLT) of the combination of irinotecan and
ZD1839 when given on this schedule.
- To characterize the pharmacokinetics and pharmacodynamics of gefitinib alone and in
combination with irinotecan and vincristine.
- To estimate the maximum tolerated dose (MTD) of gefitinib in combination with
escalating intravenous irinotecan by using selective intestinal decontamination with
oral cefixime or cefpodoxime to prevent diarrhea.
- To estimate the MTD of vincristine (MTD) in combination with gefitinib and irinotecan.
Details of Treatment Interventions
First Cohort:
Standard dose escalation, starting at ZD1839 150 mg/m2/day for 21 days in combination with
irinotecan 15mg/m2/day on a daily x 5 for two consecutive week schedule. Dose-limiting
diarrhea was seen in this cohort. ZD scheduled was reduced to 12 days. The first dose level
(1a) consisted of ZD1839 112.5mg/m2/day for 12 days + irinotecan 15mg/m2/day daily x 5 x 2
and was found to be the MTD in this cohort.
Second Cohort:
Cefixime then added at 4 additional subjects were enrolled at dose level 1c, consisting of
ZD1839 at 112mg/m2/day + irinotecan 20mg/m2/day + cefixime 8 mg/kg/day administered once
daily, beginning on day -1, and continued to day 14.
Third Cohort:
Irinotecan/ZD1839/Vincristine/Cefixime- Cefixime 8 mg/kg/day administered once daily,
beginning on day -1, and continued to day 14, with a maximum dose of 400 mg daily +
gefitinib 112.5 mg/m2 orally, daily for 12 days and irinotecan at 15 mg/m2 daily x 5 x 2 +1
mg/m2 (maximum 2mg/dose) on days 1 and 8 with escalating dose of VCR as tolerated.
Inclusion Criteria:
- Younger than 22 years of age.
- Histologic verification of solid tumor malignancy at original diagnosis.
- Has disease considered refractory to conventional therapy or no conventional therapy
exists.
- Adequate performance status, bone marrow, liver and kidney function.
- Patients must not have had any previous allergic reactions to penicillin or
cephalosporins
Exclusion Criteria:
- Known severe hypersensitivity to ZD1839 or any of the excipients of this product
- Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital,
or St John's Wort, and CYP3A4 inhibitors
- Treatment with a non-approved or investigational drug within 30 days before Day 1 of
trial treatment.
- Incomplete healing from previous oncologic or other major surgery
- Pregnant or breast-feeding
- Patients who have an uncontrolled infection
- Any evidence of clinically active interstitial lung disease (patients with chronic
stable radiographic changes who are asymptomatic need not be excluded).
- As judged by the investigator, any evidence of uncontrolled systemic disease (e.g.,
unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
- Evidence of any other significant clinical disorder or laboratory finding that makes
is undesirable for the subject to participate in the trial.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose limiting toxicities
Outcome Time Frame:
Within the first 30 days of completion of first cycle
Safety Issue:
Yes
Principal Investigator
Wayne Furman, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
St. Jude Children's Research Hospital
Authority:
United States: Food and Drug Administration
Study ID:
ZD1839
NCT ID:
NCT00186979
Start Date:
May 2003
Completion Date:
March 2010
Related Keywords:
- Solid Tumors
- Refractory Childhood Solid Tumors
- Neoplasms
Name | Location |
|---|---|
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
