Study of ZD1839 Combined With Irinotecan and Vincristine in Pediatric Patients With Refractory Solid Tumors

This study has been completed.
Sponsor:
Collaborators:
AstraZeneca
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00186979
First received: September 12, 2005
Last updated: October 3, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Drug: Irinotecan, ZD1839, Vincristine, Cefixime, Cefpodoxime.
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Dose limiting toxicities [ Time Frame: Within the first 30 days of completion of first cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: May 2003
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Drug: Irinotecan, ZD1839, Vincristine, Cefixime, Cefpodoxime.
See Detailed Description section for details of treatment interventions.

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

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00186979

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
AstraZeneca
Investigators
Principal Investigator: Wayne Furman, M.D. St. Jude Children's Research Hospital
  More Information

Additional Information:
Publications:
Effect of gefitinib on the systemic dispositon of intravenous irinotecan (IRN) in pediatric patients with refractory solid tumors. L.C. Iacono, W.L. Furman, K.R. Crews, J.C. Panetta, B.B. Freeman, N.C. Daw, C.F. Stewart. Proceedings of ASCO. Vol 22, No 14S, 2004:2011.

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00186979     History of Changes
Other Study ID Numbers: ZD1839
Study First Received: September 12, 2005
Last Updated: October 3, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Refractory Childhood Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Vincristine
Irinotecan
Gefitinib
Cefpodoxime
Cefpodoxime proxetil
Cefixime
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014