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

Alternate Title

ISIS 3521 in Treating Patients With Refractory or Recurrent High-Grade Astrocytomas

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NABTT-9706 JHOC-NABTT-9706

Objectives

I. Determine the objective response to ISIS 3521 in patients with refractory 
or recurrent high grade astrocytomas.

II. Determine the time to tumor progression in these patients.

III. Characterize the safety profile of ISIS 3521 in these patients.

Entry Criteria

Disease Characteristics:

Histologically proven refractory or recurrent anaplastic astrocytoma,
anaplastic oligodendroglioma, or glioblastoma multiforme previously treated
with radiation and/or chemotherapy
  Patients with previous low grade glioma who have progressed after
   radiotherapy and/or chemotherapy are eligible 
  Measurable refractory or recurrent supratentorial malignant glioma by CT or
   MRI imaging within 2 weeks of study
  

Prior/Concurrent Therapy:

Biologic therapy:
 At least 4 weeks since biological therapy and recovered

Chemotherapy:
 At least 3 weeks since chemotherapy and recovered
 At least 6 weeks since nitrosourea therapy and recovered
 No more than 2 prior chemotherapy regimens

Endocrine therapy:
 Concurrent steroid therapy must be stable

Radiotherapy:
 At least 3 months since radiotherapy and recovered

Surgery:
 Not specified

Other:
 At least 4 weeks since investigational new drug or therapeutic device therapy
 No prior protein kinase C inhibitor therapy
 No concurrent administration of therapeutic heparin doses
 Concurrent coumadin therapy allowed

Patient Characteristics:

Age:
 18 and over

Performance Status:
 Karnofsky 60-100%

Life Expectancy:
 Greater than 2 months

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 9 g/dL

Hepatic:
 Bilirubin no greater than 1.5 mg/dL
 SGOT and SGPT no greater than 4 times upper limit of normal
 
Renal:
 Creatinine no greater than 1.5 mg/dL

Other:
 Not pregnant or nursing
 Effective contraceptive method used by fertile patients during and for 6
  months after completing therapy
 No concurrent serious infection or medical illness
 No concurrent or prior malignancies for at least 5 years, except:
  Curatively treated basal cell skin carcinoma
  Curatively treated squamous cell skin carcinoma
  Carcinoma in situ of the cervix
  Carcinoma in situ of the breast

Expected Enrollment

A maximum of 33 patients will be accrued.

Outline

This is a two stage study.

Patients receive continuous intravenous ISIS 3521 for 21 days, followed by 7 
days of rest. Patients continue on treatment until unacceptable toxic effects 
or disease progression is observed.

If, after administration of the first 2 cycles of study medication, there is 
no evidence of grade 3 or 4 toxicity, an increased dose of intravenous ISIS 
3521 may be administered.

Patients will be followed every 2 months until death.

Grossman SA, Alavi JB, Supko JG, et al.: Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. Neuro-oncol 7 (1): 32-40, 2005.[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