ZD1839 and Oral Irinotecan in Treating Young Patients With Refractory Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00132158
First received: August 17, 2005
Last updated: April 16, 2012
Last verified: April 2012
  Purpose

The purpose of this Phase I study is to find the largest dose of the drug irinotecan, in combination with ZD1839, that can be given safely to children and to learn the good and bad effects. Studies performed in the laboratory have shown that ZD1839 helps make available the orally administered irinotecan. In this study the intravenous (given into the vein) formula of irinotecan will be given orally on days 1-5 and days 8-12. The dose of ZD1839 will be a fixed dose and will be administered orally on days 1-12. Each course of treatment will consist of 21 days. The administration of irinotecan on day 12 of course 1 and day 2 of course 2 will be an intravenous administration. All other doses and subsequent courses will consist of an orally administered dose.


Condition Intervention Phase
Glioblastoma
Rhabdomyosarcomas
Neuroblastoma
Osteosarcoma
Drug: Irinotecan (Camptosar), Gefitinib (Iressa)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Finding Study (Phase I) of the Combination of ZD1839 (Iressa®) and an Oral Formulation of Irinotecan (Camptosar™) in Children With Refractory Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To estimate the maximum tolerated dose (MTD) of the intravenous formulation of irinotecan given orally in combination with a fixed dose of oral gefitinib. [ Time Frame: Within the first 30 days of completion of first cycle of chemotherapy. ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: September 2005
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Drug: Irinotecan (Camptosar), Gefitinib (Iressa)
See Detailed Description for treatment plan.

Detailed Description:

This is a phase I study to estimate the maximum tolerated dose and the dose limiting toxicities of the intravenous formulation of irinotecan given orally in combination with a fixed dose of oral gefitinib. This trial will use the EWOC method, which is an adaptive dose escalation scheme. The method is fully adaptive and makes use of all the information available at the time of each dose assignment, and directly addresses the ethical need to control the probability of overdosing. It is designed to approach the maximum tolerated dose (MTD) as fast as possible.

In this study the intravenous formulation of irinotecan will be given orally on days 1-5 and days 8-12 (dose level begins at 5 mg/m2 ). One patient will be treated at each dose level of irinotecan until moderate toxicity is observed. At the level where moderate toxicity is observed, the cohort size will be increased to 2 patients. Dosages will then be increased until the development of DLT as guided by the EWOC model. The estimated MTD will be continually reassessed using all data from preceding patients. The toxicity data of all patients enrolled in the trial are used to update the dose-toxicity relationship and to guide the next escalation/de-escalation. The calculation will be carried out with EWOC software. Patients will be enrolled and the dose assigned is determined based on previous participants' toxicity. The dose of ZD1839 will be a fixed dose and will be administered orally on days 1-12 - [150 mg/m2 (maximum 250 mg)] Each course of treatment will consist of 21 days. The administration of irinotecan on day 12 of course 1 and day 2 of course 2 will be an intravenous administration. All other doses and subsequent courses will consist of an orally administered dose.

Secondary Objectives Include:

  • To describe dose-limiting toxicities (DLTs) of the combination of oral irinotecan and ZD1839 and to define their duration and reversibility.
  • To investigate the pharmacokinetics of oral irinotecan and ZD1839 when given in combination in children with recurrent malignant solid tumors.
  • To describe the relationship between pharmacokinetic parameters and toxicity.
  • To describe any antitumor effects within the confines of a phase I study.
  • To examine tumor expression of ErbB1 and/or ABCG2 with respect to pharmacokinetics and response.
  • To examine the pharmacogenetic determinants of ZD1839 and irinotecan pharmacokinetics and pharmacodynamics.
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient's age is less than or equal to 21 years at the time of study entry.
  • Patient has a histologically or pathologically confirmed diagnosis of a recurrent solid tumor that did not respond to standard treatment or one for which there is no known therapy.
  • Patient has adequate performance status, along with adequate function of the liver, kidney and bone marrow.
  • Must have recovered from chemotherapy
  • No active GVHD nor treatment for GVHD

Exclusion Criteria:

  • Patient is receiving other cytotoxic or investigational drug or has evidence of another active illness
  • Active diarrhea
  • Active intercurrent serious or uncontrolled illness
  • Pregnant or lactating
  • Concomitant use of medications that may interact with study drugs
  • Active infection
  • Known history of life-threatening allergy or hypersensitivity to camptothecin Active interstitial lung disease
  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: NCT00132158

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: Lisa M McGregor, MD, PhD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00132158     History of Changes
Other Study ID Numbers: POCPZD, IRUSIRES0181
Study First Received: August 17, 2005
Last Updated: April 16, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Astrocytoma
Glioma
Myosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Muscle Tissue
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014