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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 1 to 25 NCI NCI-91-C-195 NCI-T91-0019N, T91-0019

Objectives

I.  Determine the MTD and dose-limiting toxicity of cyclopentenylcytosine 
(CPE-C) administered as a 24-hour infusion using a pharmacologically guided 
dose escalation scheme in children with refractory cancer.

II.  Determine the incidence and severity of other toxicities of CPE-C as 
administered in these patients.

III.  Determine a safe and tolerable dose for 24-hour infusion to be used in 
Phase II trials.

IV.  Determine the pharmacokinetics of a 24-hour infusion of CPE-C in children.

Entry Criteria

Disease Characteristics:

Histologically proven malignancy that is refractory to
conventional therapy

Prior/Concurrent Therapy:

Biologic therapy:
  Recovery from toxicity of prior immunotherapy required

Chemotherapy:
  At least 2 weeks since prior myelosuppressive chemotherapy (6
     weeks for nitrosoureas)
  Recovery from toxicity of prior chemotherapy required

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior extensive radiotherapy (e.g., hemipelvic or
     craniospinal)
  No prior total-body irradiation in conjunction with bone
     marrow transplantation
  Recovery from toxicity of prior radiotherapy required

Surgery:
  Not specified

Patient Characteristics:

Age:
  1 to 25

Performance status:
  ECOG 0-2

Life expectancy:
  At least 8 weeks

Hematopoietic:
  AGC greater than 1,500
  Platelets greater than 100,000
  Hb greater than 9 g/dl

  Granulocytopenia, anemia, or thrombocytopenia secondary to
  bone marrow involvement with leukemia is allowed

Hepatic:
  Bilirubin less than 2.0 mg/dl
  SGPT less than 2 x normal

Renal:
  Creatinine less than 1.5 mg/dl

Other:
  No significant systemic illness (e.g., infection)
  No pregnant or nursing women

Expected Enrollment

Approximately 15-20 patients will be entered over 1 year.  At least 3 patients 
must be evaluable for hematologic toxicity in each cohort (at least 6 patients 
in expanded cohorts).

Outline

Nonrandomized study.

Single-agent Chemotherapy.  Cyclopentenylcytosine, CPE-C, NSC-375575.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Frank Balis, MD, Protocol chair		Ph: 301-496-0085 Email: balisf@nih.gov