A Phase I Study of Oral Topotecan in Subjects with Cancer and Impaired Renal Functio

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
2. Age 18 years or older.
3. A performance status score of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale.
4. Histologically- or cytologically-confirmed advanced solid tumours.
5. Failed conventional therapy for their tumor type; or subjects who have a tumor type for which no standard effective therapy exists; or subjects for whom single-agent topotecan therapy is suitable.
6. Completion of a 24-hour urine collection within 14 days prior to the first dose to calculate the creatinine clearance value and determine the renal impairment category.
7. Documentation of a stable renal function for at least 14 days prior to first scheduled dose using the Cockcroft-Gault formula, and at least 2 serum creatinine values separated by a minimum of 7 days. Stable renal function is defined as:
a. < or = 25% change of CrCl<40 mL/min
b. < or = 10 mL/min change for CrCl > or = 40mL/min
NOTE: Documentation of stable renal function will NOT be required if the 24-hour urine collection to determine the renal impairment category is completed within 7 days prior to the first dose.

Exclusion Criteria

1. Currently undergoing dialysis.
2. Pregant or lactating
3. Women of childbearing potential who refuse to either abstain from secual intercourse or practice adequate contraception defined as:
a. complete abstinence from sexual intercourse for 14 days before exposure to study drug, continuing throughout the clinical trial, and for a period of at least 14 days after the last dose of study drug;
b. oral contraceptives or intrauterine device [IUD] initiated at least 3 months prior to start of the study medication;
c. double barrier such as diaphragm plus spermicide;
d. vasectomized partner who is sterile prior to the female subject*s entry and is the sole sexual partner of that female.
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).
4. Male subjects with female partners of childbearing potential who have not had a prior vasectomy or if both the male subject and the female partner refuse to:
use adequate contraception (as described above) beginning 14 days before exposure to study drug, continuing throughout the clinical trial, and for a period of 3 months after the last dose of study drug.
5. Uncontrolled emesis, regardless of etiology.
6. Bilirubin > 1.5 X ULN.
7. SGOT/AST, SGPT/ALT and alkaline phosphatase > 2 times the upper limit of normal (ULN) if liver metastases cannot be visualized by abdominal computed tomography (CT) or magnetic resonance imaging (MRI). If liver metastases are present, subjects with <5 times ULN are eligible to participate, following discussion with and approval from a GSK Medical Monitor.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Adverse events (AEs) and changes in laboratory values.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Maximum plasma concentration (Cmax) and area under the concentration-time<br /><br>curve (AUC) of oral topotecan (total topotecan and topotecan lactone).<br /><br>• Apparent oral clearance (CL/F), time of maximum plasma concentration (tmax),<br /><br>apparent oral volume of distribution (Vd/F), half-life (t*), fraction excreted<br /><br>(Fe), and renal clearance (CLr).</p><br>