Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	5 to 18	Other, Pharmaceutical / Industry	KSB-311P/CI/001 MUSC-10550, NCT00052624

Objectives

1. Determine the maximum tolerated dose of intratumoral transferrin-CRM107 in pediatric patients with progressive or recurrent glioblastoma multiforme or anaplastic astrocytoma.
2. Determine the safety of this drug in these patients.
3. Determine the efficacy of this drug in these patients.
4. 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.

Entry Criteria

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

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

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/mm³
• Absolute neutrophil count at least 1,000/mm³

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Xenova Biomedix Limited

Patrick Rossi, MD, Protocol chair		Ph: 856-273-6057

Registry Information
Official Title		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
Trial Start Date		2002-07-26
Registered in ClinicalTrials.gov		NCT00052624
Date Submitted to PDQ		2002-10-25
Information Last Verified		2004-04-27

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