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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00483860
First received: June 5, 2007
Last updated: October 25, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Lung Cancer, Small Cell
Drug: Topotecan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Oral Topotecan in Subjects With Cancer and Impaired Renal Function

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Comparison of blood levels of topotecan following oral and IV dosing; [ Time Frame: blood samples will be drawn on Day 1 and Day 8 of Courses 1 and 2. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assessment of clinical laboratory tests, cardiac monitoring and disease progression. Comparison of blood levels of topotecan when taken orally with and without food; [ Time Frame: blood samples will be drawn on Day 1 ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: June 2007
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topotecan
once a day
Drug: Topotecan
once a day
Other Name: Topotecan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00483860

Locations
United States, Arizona
GSK Investigational Site
Scottsdale, Arizona, United States, 85258
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
GSK Investigational Site
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00483860     History of Changes
Other Study ID Numbers: SKF104864/722
Study First Received: June 5, 2007
Last Updated: October 25, 2012
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration
Korea: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Cancer
Solid tumor,
normal renal function
renal impairment,
prior platinum-based chemotherapy,

Additional relevant MeSH terms:
Lung Neoplasms
Renal Insufficiency
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Kidney Diseases
Urologic Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014