Combination of Irinotecan and Temozolomide in Children With Brain Tumors.

Phase 2 Single-Arm, Open Label Study Of Irinotecan In Combination With Temozolomide In Children With Recurrent Or Refractory Medulloblastoma And In Children With Newly Diagnosed High-Grade Glioma.

This study will assess the rate of objective confirmed tumor response of irinotecan in combination with temozolomide in children with recurrent or refractory medulloblastoma and in children with newly diagnosed high-grade glioma.

Study Overview

• Status: Completed
• Conditions: Glioma; Medulloblastoma
• Intervention / Treatment: Drug: Irinotecan; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Pfizer Investigational Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Pfizer Investigational Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Pfizer Investigational Site
• Belgium
  • Gent, Belgium, 9000
    • Pfizer Investigational Site
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Pfizer Investigational Site
  • Koebenhavn OE, Denmark, 2100
    • Pfizer Investigational Site
• France
  • Angers, France, 49000
    • Pfizer Investigational Site
  • Bordeaux, France, 33000
    • Pfizer Investigational Site
  • Lille, France, 59020
    • Pfizer Investigational Site
  • Lyon Cedex 08, France, 69373
    • Pfizer Investigational Site
  • Marseille, France, 13385
    • Pfizer Investigational Site
  • Paris, France, 75005
    • Pfizer Investigational Site
  • Villejuif, France, 94805
    • Pfizer Investigational Site
• Italy
  • Padova, Italy, 35100
    • Pfizer Investigational Site
• Poland
  • Warszawa, Poland, 04-730
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Pfizer Investigational Site
  • Madrid, Spain, 28009
    • Pfizer Investigational Site
  • Sevilla, Spain, 41013
    • Pfizer Investigational Site
  • Valencia, Spain, 46026
    • Pfizer Investigational Site
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Pfizer Investigational Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Pfizer Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Pfizer Investigational Site
  • Leeds, United Kingdom, LS9 7TF
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M27 4HA
    • Pfizer Investigational Site
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Pfizer Investigational Site
  • Nottingham, United Kingdom, NG7 2UH
    • Pfizer Investigational Site
  • Sutton, United Kingdom, SM2 5PT
    • Pfizer Investigational Site
  • Hampshire
    • Soouthampton, Hampshire, United Kingdom, SO16 6YD
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cohort 1: Recurrent or refractory medulloblastoma in which current standard treatment approaches have failed; biopsy is not required for recurrent disease.
• Cohort 2: Newly-diagnosed high-grade glioma (World Health Organization [WHO] grade 3 or 4)
• Life expectancy ≥ 3 months

Exclusion Criteria:

• Diagnosis of brainstem glioma
• Concurrent administration of any other anti-tumor therapy
• Pre-existing uncontrolled diarrhea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Temozolomide + Irinotecan	Drug: Irinotecan; Irinotecan 10 mg/m^2 per day on days 1-5 and days 8-12 in repeated 3 week cycles; Drug: Temozolomide; Temozolomide 100-125 mg/m^2 daily on days 1-5 in repeated 3 week cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response of Complete Response or Partial Response	Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). CR persisted on repeat imaging study at least (≥) 4 weeks after initial documentation of response. PR, for bidimensionally measurable disease, was a decrease by ≥50% of the sum of the products of the largest perpendicular diameters of all measurable lesions as determined by 2 observations not less than 4 weeks apart. Best overall response recorded any time while the participant was receiving treatment. External Response Review Committee (ERRC) assessment.	Baseline to 1 Year (medulloblastoma), Baseline to 6 Weeks (high-grade glioma)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response of Complete Response or Partial Response, Investigator's Assessment	Percentage of participants with objective response based assessment of confirmed CR or confirmed PR. CR persisted on repeat imaging study ≥4 weeks after initial documentation of response. PR, in case of bidimensionally measurable disease, was a decrease by ≥50% of the sum of the products of the largest perpendicular diameters of all measurable lesions as determined by 2 observations not less than 4 weeks apart. Best overall response could be recorded any time while the participant was receiving treatment. Investigator's assessment.	Baseline to 1 Year (medulloblastoma), Baseline to 6 Weeks (high-grade glioma)
Duration of Response	Median duration (50%) of tumor response for participants with objective disease response: who have not progressed or died due to any cause; with a response and subsequent progression or death due to any cause for duration of response (DR). DR was defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurred first. DR (calculated in Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7. Investigator's assessment.	Baseline to Date of Tumor Response (Up to 1 Year)
Time to Treatment Failure (TTF)	TTF was defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD), the date of treatment discontinuation except completion of treatment, or date of death due to cancer. Investigator's assessment.	Baseline to Date of Treatment Failure (Up to 1 Year)
Time to Tumor Progression (TTP)	TTP was defined as the time in months from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever came first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7 multiplied by 4.33. Tumor progression was determined from oncologic assessment data (where data met the criteria for PD). Investigator's assessment.	Baseline to Date of Progression (Up to 1 Year)
Overall Survival (OS)	Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7 multiplied by 4.33. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). Investigator's assessment.	Baseline to Date of Death (Up to 1 Year After Treatment)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: November 27, 2006
• First Submitted That Met QC Criteria: November 27, 2006
• First Posted (Estimate): November 28, 2006

Study Record Updates

• Last Update Posted (Estimate): April 18, 2012
• Last Update Submitted That Met QC Criteria: April 16, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Glioma; Medulloblastoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Temozolomide; Irinotecan
• Other Study ID Numbers: A5961166