Phase I Study of Intrathecal Topotecan

Launched by NATIONAL CANCER INSTITUTE (NCI) · Dec 9, 2002

Keywords

ClinConnect Summary

The purpose of this study is to determine the qualitative and quantitative toxicity of intrathecal topotecan, a topoisomerase I inhibitor, in patients with meningeal malignancies refractory to conventional therapy (radiation therapy and chemotherapy). A safe dose of topotecan that can be recommended for intrathecal administration in subsequent phase II studies will be established in a limited dosage escalation schedule. The CSF pharmacokinetics of intrathecal topotecan will also be studied. Topotecan will be administered intrathecally on a bi-weekly basis for four to six weeks, followed by ...

Gender

ALL

Eligibility criteria

• DISEASE CHARACTERISTICS:
• • Leukemia, lymphoma, or solid tumor with overt meningeal involvement considered refractory to conventional therapy.
• • CSF leukemic cell count at least 5 per cubic millimeter with evidence of blast cells on cytospin or cytology required for leukemia and lymphoma patients.
• • Tumor cells on cytospin or cytology or measurable meningeal disease on CT or MRI required for patients with solid tumors.
• • No clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow as documented by indium-111- or technetium-99-DPTA flow study.
• PRIOR/CONCURRENT THERAPY:
• • At least 1 week since CNS therapy.
• • Biologic Therapy: Recovery from toxic effects of prior immunotherapy required.
• Chemotherapy:
• • Recovery from toxic effects of prior chemotherapy required.
• • No concomitant therapy to treat meningeal malignancy (intrathecal or systemic).
• • Concomitant chemotherapy to control systemic disease or bulk CNS disease allowed except: Investigational agents. Agents that penetrate the CNS (e.g., high-dose methotrexate, thiotepa, high-dose cytarabine, fluorouracil, intravenous mercaptopurine).
• • Agents known to have serious unpredictable CNS side effects.
• • Endocrine Therapy: Not specified.
• • Radiotherapy: Recovery from toxic effects of prior radiotherapy required. Patient eligible if flow restored following focal radiotherapy to the blockage site.
• • Surgery: Not specified.
• PATIENT CHARACTERISTICS:
• • Age: 3 and over (older patients giving consent will be enrolled before the very young, if possible).
• • Performance status: ECOG 0-2.
• • Life expectancy: At least 8 weeks.
• • Hematopoietic: See Disease Characteristics.
• • Hepatic: Bilirubin less than 2.0 mg/dL, SGPT less than 3 times normal.
• • Renal: Creatinine less than 1.5 mg/dL.
• • Metabolic: Serum electrolytes (including calcium and phosphate) normal.
• • Other: No significant systemic illness (e.g., infection). Not pregnant or lactating.