Topotecan Pharmacokinetic Characterization Study

A Phase I Study to Characterize the Pharmacokinetics of 4 mg/m2 Weekly Intravenous Topotecan in Patients With Cancer

A multi-center, open label, single dose Phase I pharmacokinetic (PK) characterization of weekly IV (intravenous) topotecan given at 4mg/m2. 15 patients will be evaluated.

Inclusion criteria:

• Written informed consent
• Performance status of 0, 1, or 2 on the Eastern Co-operative Oncology Group (ECOG) Scale
• Predicted life expectancy of at least 3 months
• Subjects with histologically or cytologically confirmed advanced solid tumors who have failed conventional therapy for their tumor type or have a tumor type for which no standard effective therapy exists; OR Patients for whom single-agent topotecan therapy is suitable
• At least 4 weeks since last chemotherapy, radiotherapy, biologic therapy or surgery
• Must be free of post-treatment side effects (with the exception of alopecia)
• No concurrent chemotherapy, biologic therapy or radiotherapy is allowed
• Hemoglobin = 9.0 g/dL
• WBC = 3,500/mm3 [= 3.5 x 109/L]
• Neutrophils = 1,500/mm3 [= 1.5 x 109/L]
• Platelets = 100,000/mm3 [= 100.0 x 109/L]
• Calculated creatinine clearance=60 mL/min using the Cockcroft-Gault formula
• Serum bilirubin < 2.0 mg/dL (34 µmol/L) AST, SGPT/ALT and alkaline phosphatase < 2 times the upper limit of normal if liver metastases cannot be visualized by abdominal computed tomography (CT) or magnetic resonance imaging (MRI scan)
• If liver metastases are present, subjects with < 5 times the upper limit of normal are eligible to participate

Exclusion criteria:

• Women who are pregnant or lactating
• Women subjects of childbearing potential who refuse to abstain from sexual intercourse or practice adequate contraception. Childbearing potential is defined as women who are not surgically sterilized (i.e. have not had a hysterectomy, bilateral oophorectomy [ovariectomy], or bilateral tubal ligation) or post-menopausal (i.e., documented absence of menses for one year prior to entry into the study).
• Men unwilling to abstain from sex or use effective contraception during the study and for 3 months following completion of topotecan treatment
• Subjects with uncontrolled emesis, regardless of etiology
• Active infection
• Concurrent severe medical problems unrelated to the malignancy, which would significantly limit full compliance with the study or expose the patient to extreme risk
• Treatment with another investigational drug within 30 days or five half-lives prior to entry into the study (whichever is longer)
• History of allergic reactions to compounds chemically related to topotecan.