Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	NABTT-9505 JHOC-NABTT-9505, NCI-T94-0168O

Objectives

I.  Determine the optimum dose and schedule of aminocamptothecin (9-AC) in 
adults with newly diagnosed supratentorial glioblastoma multiforme who are 
taking anticonvulsants that affect hepatic metabolic pathways and in those who 
do not take such anticonvulsants.

II.  Estimate the maximum tolerated dose of 9-AC in these two patient groups 
by the Continual Reassessment Method.

III.  Assess the response rate to 9-AC administered as a 72-hour infusion 
prior to radiotherapy in these patients.

IV.  Assess the proportion of patients surviving at least 1 year following 
institution of therapy.

V.  Estimate the duration of disease-free progression and survival with this 
treatment regimen.

VI.  Correlate important pharmacokinetic parameters, including steady-state 
9-AC levels and 9-AC clearance, with toxicity and/or drug activity in this 
patient population.

VII.  Determine the toxicity of cranial irradiation following chemotherapy 
with 9-AC.

Entry Criteria

Disease Characteristics:

Histologically confirmed, newly diagnosed, supratentorial grade IV astrocytoma
(glioblastoma multiforme)

Measurable, contrast-enhancing tumor on postoperative, pretreatment magnetic
resonance imaging (preferred) or computed tomography
  Scan within 48 hours of surgery if possible

Prior/Concurrent Therapy:

No prior radiotherapy, chemotherapy, hormonal therapy, or biologic therapy for
brain tumor

Glucocorticoids allowed

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky 60%-100%

Hematopoietic:
  ANC at least 1,500
  Platelets at least 100,000

Hepatic:
  Bilirubin no greater than 1.5 mg/dL
  Transaminases no greater than 4 times normal

Renal:
  Creatinine no greater than 1.7 mg/dL

Other:
  No prior hemorrhagic cystitis
  No serious infection
  No other illness that precludes therapy
  No concomitant malignancy except curatively treated:
     Cervical carcinoma in situ
     Basal cell skin carcinoma
  No pregnant or nursing women
  Effective contraception required of fertile patients

Expected Enrollment

For the Phase II portion of the study, if at least 1 response is seen in the 
first 10 patients, 19 additional patients will be entered.

Outline

Single-Agent Chemotherapy followed by Radiotherapy.  Aminocamptothecin, 9-AC, 
NSC-603071; followed by cranial irradiation using megavoltage equipment (Co60 
to 10 MV photons).

Hochberg F, Grossman SA, Mikkelsen T, et al.: Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma. NABTT CNS Consortium. Neuro-oncol 2 (1): 29-33, 2000.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Stuart Grossman, MD, Protocol chair		Ph: 410-955-8837 Email: Grossman@jhmi.edu