Clinical trial NCT00361803: Topotecan Pharmacokinetic Characterization Study
Official title: A Phase I Study to Characterize the Pharmacokinetics of 4 mg/m2 Weekly Intravenous Topotecan in Patients With Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: chemotherapy
recurrent
refractory
research
cancer
pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-08-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: CL and Vss of total topotecan
timeFrame: Predose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.5, 4.5, 6.5, 8.5, 12, and 24 hours after the start of infusion on Day 1
Secondary outcomes:
measure: Cmax tmax t½ AUC(0-t) AUC(0-8) of total topotecan. Safety and tolerability will also be evaluated.
timeFrame: Up to 77 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kurtis, KK, Jewell RC, Hartney JT, Griffin, PP, et al. Phase I study to characterize pharmacokinetics (PK) of topotecan (T) at 4 mg/m2 administered weekly as a 30-minute IV infusion. J Clin Oncol 26: 2008 (May 20 suppl; abstr 13551).