Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Alternate Title

Aminocamptothecin in Adults with Recurrent or Progressive Malignant Glioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	over 18	NCI	NABTT-9506 MGH-NABTT-9506, NCI-T94-0169O

Objectives

I.  Determine the optimum dose and schedule of aminocamptothecin (9-AC) in 
adults with recurrent or progressive malignant glioma 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 in 
these patients.

IV.  Determine the time to progression.

V.  Correlate steady-state 9-AC levels and 9-AC clearance with toxicity and/or 
drug activity.

VI.  Assess the toxicity of 9-AC in these patients.

Entry Criteria

Disease Characteristics:

Histologically proven anaplastic astrocytoma or glioblastoma multiforme
  Progressive OR
  Recurrent following radiotherapy or chemotherapy

Tumor measurable by MRI or CT

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No more than 1 prior chemotherapy regimen
  No prior topoisomerase I inhibitor (e.g., topotecan, irinotecan,
     aminocamptothecin)
  At least 3 weeks since chemotherapy (6 weeks since nitrosoureas) and
     recovered

Endocrine therapy:
  Not specified

Radiotherapy:
  At least 2 months since radiotherapy and recovered

Surgery:
  Not specified

Other:
  No concurrent investigational agents

Patient Characteristics:

Age:
  Over 18

Performance status:
  Karnofsky 60%-100%

Life expectancy:
  Greater than 2 months

Hematopoietic:
  WBC at least 3,500
  ANC at least 1,500
  Platelets at least 100,000
  Hb at least 9 g/dL

Hepatic:
  Bilirubin no greater than 1.5 mg/dL
  AST less than 4 times the upper limit of normal
  PT/PTT normal

Renal:
  Creatinine no greater than 1.5 mg/dL OR
  Creatinine clearance greater than 60 mL/min OR
  BUN less than 50 mg/dL
  No history of hemorrhagic cystitis

Cardiovascular:
  No uncontrolled hypertension
  No angina pectoris
  No uncontrolled cardiac dysrhythmia

Other:
  No hemorrhagic cystitis
  No serious infection
  No other illness that precludes chemotherapy
  No pregnant or nursing women
  Effective contraception required of fertile women
  No prisoners

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.  If only 1 of the 
first 10 patients or 9 or more of the first 10 patients experience DLT, 3 
patients/dose will be entered in the Phase I study.  As of 02/96, the study 
for Group A patients has moved to the Phase I CRM design; Group B patients 
remain at the initial Phase II portion of the study.

Outline

Single-Agent Chemotherapy.  Aminocamptothecin, 9-AC, NSC-603071.

Grossman SA, Hochberg F, Fisher J, et al.: Increased 9-aminocamptothecin dose requirements in patients on anticonvulsants. NABTT CNS Consortium. The New Approaches to Brain Tumor Therapy. Cancer Chemother Pharmacol 42 (2): 118-26, 1998.[PUBMED Abstract]

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

Fred Hochberg, MD, Protocol chair		Ph: 617-726-8657; 877-726-5130