Topotecan and Vinorelbine in Treating Patients With Recurrent Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as topotecan and vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of topotecan when given together with vinorelbine in treating patients with recurrent lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of topotecan when combined with vinorelbine ditartrate in patients with recurrent lung cancer. Secondary Assess the response and stable disease rates and the time to disease progression among treated patients. OUTLINE: This is a dose-escalation study of topotecan. Patents receive vinorelbine ditartrate IV over 8-10 minutes and topotecan IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Official Title
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A Phase I Study of Topotecan in Combination With Vinorelbine in Recurrent Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: topotecan hydrochloride
* Drug: vinorelbine tartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed lung cancer All histologic types eligible Recurrent or progressive disease after ≥ 1 prior chemotherapy regimen with or without radiotherapy PATIENT CHARACTERISTICS: ECOG performance status (PS) ≤ 2 Karnofsky PS ≥ 60% Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Total bilirubin ≤ 1.5 mg/dL Creatinine ≤ 1.5 mg/dL Not pregnant or nursing Fertile patients must use effective contraception No other active invasive malignancy No uncontrolled illness including, but not limited to: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia No psychiatric illness/social situation that would limit compliance with study requirements No history of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan or vinorelbine ditartrate PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 2 weeks since prior radiotherapy No prior therapy with topotecan or vinorelbine ditartrate No chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C) Recovered from agents administered > 4 weeks earlier No other concurrent investigational agents No concurrent palliative radiotherapy No other concurrent anticancer therapies or agents No concurrent hormones or other chemotherapy except for the following: Steroids for adrenal failure Hormones for nondisease-related conditions (e.g., insulin for diabetes) Intermittent dexamethasone as an antiemetic

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vinorelbine + topotecan<br> | Drug: topotecan hydrochloride<br> <br> Drug: vinorelbine tartrate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | Cycle 1 (up to day 21) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | while on study, at the end of each 3 week cycle | 
| stable disease rate |  | while on study, at the end of each 3 week cycle | 
| time to progression |  | from start of treatment to day of documented progression or death, whichever comes first, up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the lung, adenosquamous cell lung cancer, bronchoalveolar cell lung cancer, combined type small cell lung cancer, intermediate type small cell lung cancer, large cell lung cancer, lymphocyte-like type small cell lung cancer, recurrent non-small cell lung cancer, recurrent small cell lung cancer, squamous cell lung cancer