Title
Immunotoxin Therapy in Treating Children With Progressive or Recurrent Glioblastoma Multiforme or Anaplastic Astrocytoma
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
Phase
Phase 1Lead Sponsor
Xenova BiomedixStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Brain and Central Nervous System TumorsIntervention/Treatment
transferrin-crm107 ...Study Participants
NoneRATIONALE: 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
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.
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
