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

Study Overview
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Brief Summary
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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.

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

Conditions
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Lung Cancer, Non-Small Cell, Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Topotecan/Docetaxel combination
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Topotecan/Docetaxel combination|nan|
|Drug: Docetaxel|nan|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HYCAMTIN, TAXOTERE, non-small cell lung cancer, NSCLC, docetaxel, topotecan, Stage IIIB/IV, Advanced