This phase I trial studies the side effects and best dose of topotecan hydrochloride when given together with doxorubicin hydrochloride in treating patients with small cell lung cancer (SCLC) that has come back after a period of improvement (relapsed) or has not responded to treatment (refractory). Drugs used in chemotherapy, such as topotecan hydrochloride and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Doxorubicin hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving topotecan hydrochloride and doxorubicin hydrochloride may be a better treatment for small cell lung cancer.
PRIMARY OBJECTIVES: I. Evaluate the safety and efficacy, in terms of clinical disease benefit, (complete or partial response and stable disease with stable or improved quality of life scores) of combination of oral topotecan (topotecan hydrochloride) when given with weekly doxorubicin (doxorubicin hydrochloride) in patients with SCLC. II. Determine the dose limiting toxicity of oral topotecan when given with weekly doxorubicin in patients with SCLC. SECONDARY OBJECTIVES: I. Estimate topoisomerase I and II levels in peripheral blood mononuclear cells and correlate with presence or absence of grades 3 and 4 hematological toxicity. II. Estimate topoisomerase I and II levels in peripheral blood mononuclear cells and correlate with efficacy. OUTLINE: This is a dose-escalation study of topotecan hydrochloride. Patients receive doxorubicin hydrochloride intravenously (IV) over 3-5 minutes on day 6 of course 1 and on days 6, 13, and 20 of courses 2-5. Patients also receive topotecan hydrochloride orally (PO) on days 1-5. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Given IV
Correlative studies
Ancillary studies
Given PO
University of Nebraska Medical Center
Omaha, Nebraska, United States
Maximum tolerated dose defined as the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience dose limiting toxicities in cohorts of 5 different doses by National Cancer Institute Common Toxicity Criteria version 3.0
The actual rates of dose limiting toxicities per dose cohort will be presented when applicable.
Time frame: Up to 6 weeks (after 2 courses)
Changes in topoisomerase I and II levels in peripheral blood mononuclear cells
The changes over time will be described and correlated with hematological toxicity and efficacy. Mean change and standard deviation over time will be computed and when possible change in topoisomerase levels over time will be compared between patients developing grade 4 hematological toxicities versus others (no toxicity or grades 1-3) or between patients developing grades 3-4 non-hematological toxicities versus others (no toxicity or grades 1-2) or between patients who responded (complete response, partial response, stable disease) versus no response or progressed using non-parametric tests.
Time frame: Baseline to up to week 16
Overall response rate
complete or partial response and stable disease
Time frame: Up to 15 weeks (after 5 courses)
Changes in quality of life levels
Measured by standard instruments and compared when possible between patients who responded versus nonresponders.
Time frame: Up to 16 weeks
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