Study of ZD1839 Combined With Irinotecan and Vincristine in Pediatric Patients With Refractory Solid Tumors
Information source: St. Jude Children's Research Hospital
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Solid Tumors
Intervention: Irinotecan, ZD1839, Vincristine, Cefixime, Cefpodoxime. (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: St. Jude Children's Research Hospital Official(s) and/or principal investigator(s):
Wayne Furman, M.D., Principal Investigator, Affiliation: St. Jude Children's Research Hospital
Overall contact:
Wayne Furman, M.D., Phone: 1-866-278-5833, Email: info@stjude.org
Summary
The purpose of this protocol is to estimate the maximum tolerated dose of gefitinib in
combination with fixed dose of irinotecan and vincristine in patients with refractory solid
tumors.
Clinical Details
Official title: A Phase I Study of ZD1839 (Iressa) in Combination With Irinotecan (Camptosar or CPT-11) and Vincristine in Pediatric Patients With Refractory Solid Tumors
Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary outcome: Dose limiting toxicities
Detailed description:
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.
Eligibility
Minimum age: N/A.
Maximum age: 21 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Wayne Furman, M.D., Phone: 1-866-278-5833, Email: info@stjude.org
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States; Recruiting
Wayne Furman, M.D., Phone: 866-278-5833, Email: Info@stjude.org
Wayne Furman, M.D., Principal Investigator
Additional Information
St. Jude Children's Research Hospital
Starting date: May 2003
Ending date: May 2009
Last updated: December 2, 2008
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