Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma

May 14, 2018 updated by: Xenova Biomedix

A Phase I Multicenter Trial Of Intratumoral/Interstitial Therapy With HN66000, NC66000 (TransMID) In Patients Between 5 and 18 Years Of Age With Progressive Or Recurrent Glioblastoma Multiforme Or Anaplastic Astrocytoma

RATIONALE: Immunotoxins can locate tumor cells and kill them without harming normal cells. Immunotoxin therapy may be an effective treatment for glioblastoma multiforme and anaplastic astrocytoma.

PURPOSE: Phase I trial to study the effectiveness of immunotoxin therapy in treating children who have progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of intratumoral transferrin-CRM107 in pediatric patients with progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma.
  • Determine the safety of this drug in these patients.
  • Determine the efficacy of this drug in these patients.
  • Compare the efficacy of this drug in patients with different histological types of tumor, degrees of transferrin receptor expression, and serum antidiphtheria antibody titer levels.

OUTLINE: This is a dose-escalation, open-label, multicenter study. Patients are assigned to 1 of 2 treatment groups by age (5-9 vs 10-18).

All patients undergo stereotactic radiosurgery for tumor biopsy and placement of 2 intratumoral silastic infusion catheters pre-loaded with transferrin-CRM107 (Tf-CRM107).

  • Group 1 (ages 5-9): Patients receive intratumoral Tf-CRM107 over 3-7 days via catheter. Treatment repeats after 6-10 weeks in the absence of unacceptable toxicity. Three cohorts of 3-6 patients receive escalating doses of Tf-CRM107 until the maximum tolerated dose (MTD) is determined.
  • Group 2 (ages 10-18): Patients receive intratumoral Tf-CRM107 as in group 1. Two cohorts of 3-6 patients receive escalating doses of Tf-CRM107 until the MTD is determined.

The MTD in both groups is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for 6 months and then every 3 months for 6 months.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868-3874
        • Children's Hospital of Orange County
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Hollings Cancer Center at Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme or anaplastic astrocytoma with the following tumor characteristics:

    • Unifocal
    • Unilateral and supratentorial
    • Diameter no greater than 3.5 cm by contrast-enhanced MRI
  • No more than 1 satellite tumor

  • Recurrent or progressive disease

    • Progressive disease defined as at least 25% increase in tumor volume by serial MRI or CT scans and/or at least 15% increase in the largest cross-sectional area of tumor as defined by the area of contrast agent enhancement

  • Must have received prior conventional treatment comprising both of the following:

    • Surgery (biopsy or debulking)
    • Radiation therapy
  • No evidence of mass effect on CT scan or MRI with more than a 5 mm midline shift and/or nausea, vomiting, reduced level of consciousness, or clinically significant papilledema

PATIENT CHARACTERISTICS:

Age

  • 5 to 18

Performance status

  • Karnofsky 60-100% OR
  • Lansky Play 50-100%

Life expectancy

  • At least 3 months

Hematopoietic

  • Platelet count at least 100,000/mm^3
  • Absolute neutrophil count at least 1,000/mm^3

Hepatic

  • Bilirubin no greater than 2.0 mg/dL
  • AST and ALT no greater than 2.5 times the upper limit of normal (ULN)
  • PT or aPTT no greater than 1.5 times ULN

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 2 months after study

  • No acute viral, bacterial, or fungal infection requiring therapy

    • Topical treatment for oral candidiasis allowed
  • No other concurrent medical condition that would preclude anesthesia

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior transferrin-CRM107

Chemotherapy

  • More than 1 month since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 3 months since prior biodegradable polymer wafers
  • No concurrent chemotherapy

Endocrine therapy

  • Must be on stable dose of steroids for 7 days prior to infusion

Radiotherapy

  • See Disease Characteristics
  • More than 3 months since prior radiotherapy
  • More than 3 months since prior stereotactic radiosurgery
  • More than 6 weeks since prior craniospinal irradiation
  • No prior brachytherapy
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • More than 1 month since prior surgery including tumor surgery or debulking
  • No other concurrent surgery

Other

  • More than 30 days since prior investigational agents
  • No other concurrent investigational therapy
  • No other concurrent anti-cancer drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xenova Biomedix

Investigators

  • Study Chair: Patrick Rossi, MD, Xenova Biomedix

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2002

Study Registration Dates

First Submitted

January 24, 2003

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

May 15, 2018

Last Update Submitted That Met QC Criteria

May 14, 2018

Last Verified

April 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MUSC-10550
  • KSB-311P/CI/001
  • CDR0000258574 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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