A Phase I Topotecan Study in Subjects With Cancer and Impaired Renal Function

Solid Tumours Clinical Trial

Official title:

A Phase I Study of Oral Topotecan in Subjects With Cancer and Impaired Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00483860
• Other study ID #: SKF104864/722
• Status: Completed
• Phase: Phase 1
• First received: June 5, 2007
• Last updated: November 8, 2017
• Start date: June 20, 2007
• Est. completion date: February 6, 2012

Study information

• Verified date: November 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the effect of renal impairment and prior platinum-based chemotherapy on the safety and blood levels of topotecan administered orally

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: February 6, 2012
• Est. primary completion date: February 6, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 tumors.

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 (refer to Appendix 8).

7. Using Cockcroft-Gault formula (refer to Appendix 6), documentation of stable renal function should be performed within 14 days of the first scheduled dose of study medication using at least 2 serum creatinine values separated by a minimum of 7 days. Stable renal function is defined as:

1. =25% change for CrCl <40 mL/min or

2. =10 mL/min change for CrCl =40 mL/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:

• Currently undergoing dialysis.

• Pregnant or lactating.

• Women of childbearing potential who refuse to either abstain from sexual intercourse or practice adequate contraception

• 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 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.

• Uncontrolled emesis, regardless of etiology.

• Bilirubin > 1.5 X ULN.

• SGOT/AST, SGPT/ALT and alkaline phosphatase >2 times the upper limit of normal (ULN) if no evidence of potentially associated metastases (e.g., liver or bone) by computed tomography (CT) or magnetic resonance imaging (MRI). If potentially associated metastases (e.g., liver or bone) are present, subjects with <5 times ULN are eligible to participate, following discussion with and approval from a GSK Medical Monitor.

Hematological values outside of acceptable ranges. Active infection. Prior anti-cancer therapy, including, but not limited to, chemotherapy (except nitrosurea or mitomycin C), radiotherapy, biologic therapy, investigational therapy or major surgery within 21 days of the first scheduled dose of study drug. Prior nitrosurea of mitomycin C chemotherapy within 6 weeks of first scheduled dose of study drug. Failure to recover to Grade 1 or better from any toxicity (except alopecia) related to prior anti-cancer therapy by Day 1, Course 1 unless agreed to by a GSK Medical Monitor and the Investigator. Clinical evidence of a gastrointestinal (GI) condition (i.e., removal of a portion of the stomach, recent GI obstruction or GI neuropathy) or taking drugs that would alter GI absorption or motility. Currently taking or will require treatment with cyclosporin A. Concurrent severe medical problems unrelated to the malignancy, which would significantly limit full compliance with the study or expose the subject to extreme risk (including major surgery within 21 days or placement of biliary stents or nephrostomy tubes within 7 days). History of allergic reactions to topotecan or compounds chemically related to topotecan (e.g., irinotecan).

Related Conditions & MeSH terms

• Renal Insufficiency
• Solid Tumours

Intervention

Drug:
• Topotecan
once a day

Locations

Country	Name	City	State
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Utrecht
United States	GSK Investigational Site	Lebanon	New Hampshire
United States	GSK Investigational Site	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of blood levels of topotecan following oral and IV dosing;		blood samples will be drawn on Day 1 and Day 8 of Courses 1 and 2.
Secondary	Assessment of clinical laboratory tests, cardiac monitoring and disease progression. Comparison of blood levels of topotecan when taken orally with and without food;		blood samples will be drawn on Day 1

External Links

•   Results for study SKF104864/722 can be found on the GSK Clinical Study Register.