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
5 Years
18 Years
Both
Brain and Central Nervous System Tumors
Trial Information
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
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.
Inclusion 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
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Patrick Rossi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Xenova Biomedix
Authority:
United States: Federal Government
Study ID:
CDR0000258574
NCT ID:
NCT00052624
Start Date:
July 2002
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- recurrent childhood cerebral astrocytoma
- Astrocytoma
- Glioblastoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Children's Hospital of Orange County | Orange, California 92668 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
