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A Phase I Study of ZD1839 (Iressa) in Combination With Irinotecan (Camptosar or CPT-11) and Vincristine in Pediatric Patients With Refractory Solid Tumors


Phase 1
N/A
21 Years
Not Enrolling
Both
Solid Tumors

Thank you

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