Topotecan Hydrochloride and Doxorubicin Hydrochloride in Treating Patients With Small Cell Lung Cancer That Has Relapsed or Not Responded to Treatment
This phase I trial is studying 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 relapsed or not responded to treatment. 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 or by stopping them from dividing. Doxorubicin hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Recurrent Small Cell Lung Cancer
Drug: doxorubicin hydrochloride
Drug: topotecan hydrochloride
Procedure: laboratory biomarker analysis
Procedure: quality-of-life assessment
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Weekly Doxorubicin and Oral Topotecan for Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)|
- Safety and efficacy of this regimen as assessed by the maximum tolerated dose (MTD) of the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience dose limiting toxicities (DLT) in cohorts of 5 different doses [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
- DLT of topotecan hydrochloride administered in combination with doxorubicin hydrochloride as assessed by the MTD of the next lowest dose level below where greater than or equal to 2/3 or 3/6 patients experience DLT in cohorts of 5 different doses [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
- Changes in topoisomerase I and II levels [ Time Frame: From baseline to week 16 ] [ Designated as safety issue: No ]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.
|Study Start Date:||February 2009|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (doxorubicin hydrochloride, topotecan hydrochloride)
Patients receive doxorubicin hydrochloride IV weekly beginning on day 6 in weeks 1-15. Patients also receive topotecan hydrochloride PO on days 1-5 in weeks 1, 4, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, and at weeks 7 and 16 to measure topoisomerase I and II levels. Patients also complete the FACT-L quality of life questionnaire at baseline, and at weeks 7 and 16.
Drug: doxorubicin hydrochloride
Other Names:Drug: topotecan hydrochloride
Other Names:Procedure: laboratory biomarker analysis
Correlative studiesProcedure: quality-of-life assessment
Other Name: quality of life assessment
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.
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) weekly beginning on day 6 in weeks 1-15. Patients also receive topotecan hydrochloride orally (PO) on days 1-5 in weeks 1, 4, 7, 10, and 13 in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, and at weeks 7 and 16 to measure topoisomerase I and II levels. Patients also complete the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life questionnaire at baseline, and at weeks 7 and 16.
After completion of study treatment, patients are followed up every 2 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00856037
|United States, Nebraska|
|University of Nebraska Medical Center||Recruiting|
|Omaha, Nebraska, United States, 68198|
|Contact: Apar K. Ganti 402-559-6210 firstname.lastname@example.org|
|Principal Investigator: Apar K. Ganti|
|Principal Investigator:||Apar Ganti||University of Nebraska|