Comparison of IV Topotecan/Docetaxel to Docetaxel Alone in Second-Line Stage IIIB/IV Non-Small Cell Lung Cancer

WEEKLY IV TOPOTECAN/DOCETAXEL COMBINATION COMPARED TO DOCETAXEL IN PATIENTS WITH PRETREATED ADVANCED NSCLC: AN OPEN-LABEL MULTICENTER RANDOMIZED PHASE III TRIAL

The purpose of this study is to compare the efficacy and safety of a weekly regimen of two FDA approved drugs in combination versus one FDA approved drug in subjects with advanced non-small cell lung cancer who have received one previous chemotherapy excluding TAXOTERE or HYCAMTIN.

Study Overview

• Status: Completed
• Conditions: Lung Cancer, Non-Small Cell; Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Topotecan/Docetaxel combination

• Study Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • GSK Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • GSK Investigational Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 5P9
      • GSK Investigational Site
    • Kitchener, Ontario, Canada, N2G 1G3
      • GSK Investigational Site
    • London, Ontario, Canada, N6A 4L6
      • GSK Investigational Site
    • Ottawa, Ontario, Canada, K1H 1C4
      • GSK Investigational Site
    • St. Catharines, Ontario, Canada, L2R 5K3
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 1X5
      • GSK Investigational Site
    • Weston, Ontario, Canada, M9N 1N8
      • GSK Investigational Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • GSK Investigational Site
    • Levis, Quebec, Canada, G6V 3Z1
      • GSK Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • GSK Investigational Site
• Poland
  • Kielce, Poland, 25-640
    • GSK Investigational Site
  • Krakow, Poland, 31-115
    • GSK Investigational Site
  • Olsztyn, Poland, 10-228
    • GSK Investigational Site
  • Poznan, Poland, 60-569
    • GSK Investigational Site
  • Szczecin Zdunowo 20, Poland, 70-891
    • GSK Investigational Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • GSK Investigational Site
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85712
      • GSK Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • GSK Investigational Site
  • California
    • Fresno, California, United States, 93720
      • GSK Investigational Site
    • Los Angeles, California, United States, 90067
      • GSK Investigational Site
    • Poway, California, United States, 92064
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80210
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5001
      • GSK Investigational Site
    • Washington, District of Columbia, United States, 20422
      • GSK Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • GSK Investigational Site
    • Boca Raton, Florida, United States, 33428
      • GSK Investigational Site
    • Lakeland, Florida, United States, 33805
      • GSK Investigational Site
    • Miami Shores, Florida, United States, 33138
      • GSK Investigational Site
    • Orange Park, Florida, United States, 32073
      • GSK Investigational Site
    • Orlando, Florida, United States, 32804
      • GSK Investigational Site
    • Stuart, Florida, United States, 34994
      • GSK Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31902
      • GSK Investigational Site
  • Illinois
    • Decatur, Illinois, United States, 62526
      • GSK Investigational Site
    • Elk Grove Village, Illinois, United States, 60007
      • GSK Investigational Site
    • Skokie, Illinois, United States, 60077
      • GSK Investigational Site
    • Urbana, Illinois, United States, 61801
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • GSK Investigational Site
    • Louisville, Kentucky, United States, 40215
      • GSK Investigational Site
    • Louisville, Kentucky, United States, 40207
      • GSK Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • GSK Investigational Site
    • Lafayette, Louisiana, United States, 70506
      • GSK Investigational Site
    • Lake Charles, Louisiana, United States, 70601
      • GSK Investigational Site
  • Maryland
    • Frederick, Maryland, United States, 21701
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • GSK Investigational Site
  • Michigan
    • Grosse Pointe Woods, Michigan, United States, 48236
      • GSK Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • GSK Investigational Site
    • Minneapolis, Minnesota, United States, 55407-3799
      • GSK Investigational Site
    • Robbinsdale, Minnesota, United States, 55422
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
    • Springfield, Missouri, United States, 65807
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • GSK Investigational Site
    • Reno, Nevada, United States, 89502
      • GSK Investigational Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10467
      • GSK Investigational Site
    • Buffalo, New York, United States, 14215-1199
      • GSK Investigational Site
    • East Syracuse, New York, United States, 13057
      • GSK Investigational Site
    • Manhasset, New York, United States, 11030
      • GSK Investigational Site
    • New Hyde Park, New York, United States, 11040
      • GSK Investigational Site
    • Nyack, New York, United States, 10960
      • GSK Investigational Site
    • Rochester, New York, United States, 14623
      • GSK Investigational Site
  • North Carolina
    • Fayetteville, North Carolina, United States, 28302-2000
      • GSK Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
  • Pennsylvania
    • Dunmore, Pennsylvania, United States, 18512
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19114
      • GSK Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • GSK Investigational Site
    • Hilton Head Island, South Carolina, United States, 29926
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • GSK Investigational Site
    • Nashville, Tennessee, United States, 37203
      • GSK Investigational Site
  • Texas
    • Irving, Texas, United States, 75038
      • GSK Investigational Site
    • Tyler, Texas, United States, 75701
      • GSK Investigational Site
  • Virginia
    • Abingdon, Virginia, United States, 24211
      • GSK Investigational Site
    • Norfolk, Virginia, United States, 23502
      • GSK Investigational Site
    • Norfolk, Virginia, United States, 23507
      • GSK Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • GSK Investigational Site
    • Tacoma, Washington, United States, 98405
      • GSK Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • GSK Investigational Site
    • Sheboygan, Wisconsin, United States, 53081
      • GSK Investigational Site
  • Wyoming
    • Casper, Wyoming, United States, 85601
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Written informed consent
• At least 18 years old
• Confirmed advanced non-small cell lung carcinoma (NSCLC)
• Received one prior chemotherapy for metastatic NSCLC excluding TAXOTERE or HYCAMTIN. In addition, subjects are allowed to have previously received a non-cytotoxic therapy, such as an endothelial growth factor receptor (EGFR) or angiogenesis inhibitor.
• Presence of either measurable or non-measurable disease by radiologic study or physical examination.
• Full recovery and at least 21 days from prior treatment for NSCLC; 42 days from treatment with mitomycin or nitrosureas and 30 days from prior non-cytotoxic therapy.
• At least 3 weeks since last major surgery (a lesser period is acceptable if deemed in the best interest of the patient).
• At least 7 days since prior radiotherapy.
• A probable life expectance of at least 3 months.
• Adequate bone marrow reserve, CBC/Platelet, kidney and liver function.

Exclusion criteria:

• Concomitant malignancies or other malignancies within the last five years.
• Symptoms of brain metastases requiring treatment with steroids.
• Active infection.
• Severe medical problems other than the diagnosis of NSCLC that would limit the ability of the subject to follow study guidelines or expose the subject to extreme risk.
• Ongoing or planned chemotherapy (other than treatment during this study), immunotherapy, radiotherapy, or investigational therapy for the treatment of NSCLC.
• Use of investigational drug within 30 days or 5 half-lives prior to the first dose of study medication.
• Women who are pregnant or lactating.
• Subjects of child-bearing potential refusing to practice adequate contraception.
• Prior treatment with or history of allergic reaction to either HYCAMTIN or TAXOTERE.
• Subjects who cannot receive steroid premedication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Time of Overall Survival	Overall survival was defined as the time from randomization to death and it occurs when all randomized participants had at least one year of follow-up past their date of randomization to treatment.	Up to one year from Day -1 (randomization)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One-year Survival	Number of participants with one-year survival were planned to be reported.	Up to one year from Day -1 (randomization)
Median Time to Progression	Time to progression is defined as the time between randomization and the first radiologically or clinically documented evidence of progression.	Up to one year from Day -1 (randomization)
Response Rate	Response rate is defined as the percentage of participants in the ITT population attaining an overall best response of complete or partial response.	Up to one year from Day -1 (randomization)
Response Duration	Response duration is defined as the time from initial radiologically documented response to the first radiologically or clinically documented sign of progression.	Up to one year from Day -1 (randomization)
Time to Response-assessed Every 8 Weeks	Time to response is defined as the time between randomization and the first radiologically documented complete or partial response.	Every 8 Weeks post randomization
Assessment of Quality of Life-assessed Every 4 Weeks	The effect of treatment regimens on participants-perceived disease status and well-being was assessed using Lung Cancer Symptom Scale (LCSS) that consists of 9 items addressing the time frame of past day: 6 measuring major symptoms for lung malignancies (loss of appetite, fatigue, cough, dyspnea, hemoptysis and pain) and 3 summation items related to total symptomatic distress, activity status and global quality of life. All items are measured by visual analogue scales (VAS) which uses 100 millimeter (mm) lines to determine the intensity of participant responses. The lowest level of symptom intensity or functional disability on the VAS is on left (none) and highest intensity is on right (as much as could be).	Every 4 Weeks post randomization
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or it is considered to be medically significant.	Up to 16 months
Number of Participants With Grade 1, 2, 3 or 4 Hematologic Toxicities	Hematology parameters included hemoglobin, hematocrit, red blood cell count, white blood cell count with differential leukocyte and platelet count. Differential to include total neutrophils, bands, lymphocytes, monocytes, eosinophil, and basophils. Recording of any hematology toxicity grade was done using National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 2.0. Higher the grade, more is the toxicity. Data for number of participants with grade 1, 2, 3 or 4 hematologic toxicities have been presented.	Up to 16 months
Number of Participants With Grade 3 or 4 Clinical Chemical Toxicities	Standard chemistry evaluation included sodium, potassium, chloride, bicarbonate, calcium, phosphorous, magnesium, blood urea nitrogen (BUN)/urea, uric acid, creatinine, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, total protein and albumin. Recording of any hematology toxicity grade was done using National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 2.0. Higher the grade, more is the toxicity. Data for number of participants with grade 3 or 4 clinical chemical toxicities have been presented.	Up to 16 months
Number of Participants With Clinically Significant Abnormal Vital Signs Data	Vital sign parameters included (blood pressure, and pulse rate after five minutes sitting, body temperature). Blood pressure and pulse rate was measured after sitting for 5 minutes. Only participants with clinically significant abnormal Vital sign data was reported.	Up to 16 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2003
• Primary Completion (Actual): August 30, 2007
• Study Completion (Actual): August 30, 2007

Study Registration Dates

• First Submitted: July 17, 2003
• First Submitted That Met QC Criteria: July 17, 2003
• First Posted (Estimate): July 18, 2003

Study Record Updates

• Last Update Posted (Actual): June 24, 2019
• Last Update Submitted That Met QC Criteria: March 29, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; Advanced; docetaxel; topotecan; Stage IIIB/IV; HYCAMTIN; TAXOTERE
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Docetaxel; Topotecan
• Other Study ID Numbers: 104864/615; 2004-002892-17 (EudraCT Number)