Liposomal SN-38 in Treating Patients With Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as liposomal SN-38, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well liposomal SN-38 works in treating patients with small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the response rate in patients with small cell lung cancer treated with SN-38 liposome that is dosed according to a UGT1A1-specific genotype. Determine the toxicity of this drug in these patients. Determine, preliminarily, overall and progression-free survival of patients treated with this drug. Determine the quality of life of patients treated with this drug. Correlate UGT1A1-specific haplotypes with toxicity of this drug in these patients. Correlate UGT1A1-specific haplotypes with outcomes of patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to length of time since prior treatment (previously untreated disease OR chemosensitive disease and ≥ 3 months since prior treatment vs refractory disease OR chemoresistant disease and < 3 months since prior treatment). Patients receive SN-38 liposome IV over 90 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response or patients with stable disease (SD) who were previously treated before study enrollment receive up to 4 additional courses of treatment. Patients with CNS-only disease progression receive whole brain radiotherapy (WBRT). After completion of WBRT, these patients also receive up to 4 additional courses of treatment. Patients with disease progression to sites other than the CNS or patients with SD who were previously untreated before study enrollment are removed from the study. Quality of life is assessed at baseline, before each treatment course, and then annually for 3 years. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: Approximately 73 patients (40 for stratum I and 33 for stratum II) will be accrued for this study within 16-19 months.

Official Title
-----------------
Phase II Trial of Liposome Encapsulated SN38 (LE-SN38) in the Treatment of Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: liposomal SN-38


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer meeting 1 of the following criteria: Previously untreated disease Extensive stage disease, as defined by any of the following: Metastatic disease outside of the chest Contralateral supraclavicular or contralateral hilar nodes that cannot be included in a single radiation port Malignant pleural effusion Previously treated disease Limited or extensive stage disease Measurable disease Lesions ≥ 1 cm and < 2 cm must be measured by spiral CT scan for pre- and post-treatment tumor assessment UGT1A1*28 genotype wt/wt (6/6 promoter TA repeats) OR wt/*28 (6/7 promoter TA repeats) No *28/*28 (7/7 promoter TA repeats) genotype No mixed histology No uncontrolled CNS metastasis Previously treated, stable CNS metastasis allowed No superior vena cava syndrome No malignant pericardial effusion No near obstruction of the trachea or main stem bronchi PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Total bilirubin < 1.5 times upper limit of normal (ULN) OR Direct bilirubin normal Renal Creatinine < 1.5 times ULN Cardiovascular No unstable angina pectoris No uncontrolled congestive heart failure No myocardial infarction within the past 3 months Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study participation No syndrome of inappropriate antidiuretic hormone secretion No ectopic adrenocorticotrophic syndrome No Lambert-Eaton myasthenic syndrome No other severe paraneoplastic syndrome No active infection requiring oral or parenteral antibiotics No other life threatening disease No other malignancy except basal cell or squamous cell skin cancer, localized prostate cancer, superficial bladder cancer, or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent filgrastim (G-CSF) during course 1 of study treatment Chemotherapy No more than 1 prior chemotherapy regimen for this malignancy Prior cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) allowed More than 21 days since prior chemotherapy Endocrine therapy Not specified Radiotherapy More than 14 days since prior radiotherapy Concurrent palliative radiotherapy allowed except radiotherapy to a solitary measured index lesion Surgery More than 21 days since prior major surgery Other No other concurrent treatment for this malignancy No other concurrent investigational treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: liposomal SN-38<br>Patients receive SN-38 liposome IV over 90 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response or patients with stable disease (SD) who were previously treated before study enrollment receive up to 4 additional courses of treatment. Patients with CNS-only disease progression receive whole brain radiotherapy (WBRT). After completion of WBRT, these patients also receive up to 4 additional courses of treatment. Patients with disease progression to sites other than the CNS or patients with SD who were previously untreated before study enrollment are removed from the study. Quality of life is assessed at baseline, before each treatment course, and then annually for 3 years. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 2 years. | Drug: liposomal SN-38<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response measured by number of responses |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  | Up to 3 years | 
| Survival time |  | Up to 3 years | 
| Change in quality of life (QOL) score over time |  | Up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
extensive stage small cell lung cancer, limited stage small cell lung cancer, recurrent small cell lung cancer