Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating extensive-stage small cell lung cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have extensive-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the response frequency of patients with extensive stage small cell lung cancer treated with topotecan, cisplatin, and etoposide and with irinotecan, cisplatin, and etoposide. Evaluate the toxic effects of these regimens in these patients. Evaluate the duration of response and survival of patients treated with these regimens. Secondary To investigate the occurrence of various breast cancer resistance protein (BCRP) alleles in patients receiving topoisomerase 1 inhibitors and their impact on clinical response and toxicity. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I (PET): Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover. Arm II (PIE): Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10. In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. ACTUAL ACCRUAL: A total of 140 patients were accrued for this study.

Official Title
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A Randomized Phase II Study: Sequencing Topoisomerase Inhibitors for Extensive Stage Small Cell Lung Cancer (SCLC): Topotecan Sequenced With Etoposide/Cisplatin, and Irinotecan/Cisplatin Sequenced With Etoposide

Conditions
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Extensive Stage Small Cell Lung Cancer

Intervention / Treatment
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* Biological: G-CSF
* Drug: Cisplatin
* Drug: Etoposide
* Drug: Irinotecan
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Extensive stage small cell lung cancer (SCLC) with measurable disease, evaluated within 2 weeks prior to randomization Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 Disease-free for >=5 years if had a prior second malignancy other than treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix Adequate hematologic, hepatic and renal function determined by the following tests, within 4 weeks prior to randomization: white blood cell (WBC) >=4000/mm3 and platelets >=100,000/mm3; bilirubin <= upper limit of normal; serum glutamic pyruvate transaminase (SGPT) or alanine transaminase (ALT) and serum glutamic oxaloacetic transaminase (SGOT) or aspartate transaminase( AST) <=2.5 x upper limit of normal if no demonstrable liver metastases or <=5 times upper limit of normal in the presence of liver metastases; Calculated creatinine clearance >=30 using the formulas in the protocol Age 18 and older Strongly advised to use an accepted and effective method of contraception Those with central nervous system (CNS) metastases were eligible if the metastases were treated without advancing symptoms prior to the initiation of chemotherapy Those receiving erythropoietin could continue to receive it EXCLUSION CRITERIA: Prior radiotherapy for lung cancer; Prior radiotherapy allowed only for central nervous system (CNS) metastases Prior chemotherapy for this disease Pregnant or lactating

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PET (Topotecan/Etoposide/Cisplatin/G-CSF)<br>Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover. | Biological: G-CSF<br>* G-CSF will be administered subcutaneously at a dose of 5 mcg/kg once a day starting on day 11 until WBC recovery > 10,000 dL.<br>* Other names: r-metHuG-CSF;Drug: Cisplatin<br>* Arm PET: 20 mg/m2 IV on days 8, 9 and 10 of each cycle following Etoposide. Arm PIE: 20 mg/m2 IV on days 1 and 8 of each cycle following Irinotecan.<br>* Other names: NSC 119875;Drug: Etoposide<br>* Arm PET: 70 mg/m2 IV over 60 minutes on days 8, 9 and 10 of each cycle. Arm PIE: 85 mg/m2 orally (divided into 2 doses, 12 hours apart) on day 3 and 10 of each cycle.<br>* Other names: NSC # 141540;Drug: Topotecan<br>* Topotecan 0.75 mg/m2 IV over 30 minutes on days 1,2 and 3 of each cycle (Arm PET only).<br>* Other names: Topotecan Formula AS;|
| Experimental: PIE (Irinotecan/Cisplatin/Etoposide)<br>Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle. | Drug: Cisplatin<br>* Arm PET: 20 mg/m2 IV on days 8, 9 and 10 of each cycle following Etoposide. Arm PIE: 20 mg/m2 IV on days 1 and 8 of each cycle following Irinotecan.<br>* Other names: NSC 119875;Drug: Etoposide<br>* Arm PET: 70 mg/m2 IV over 60 minutes on days 8, 9 and 10 of each cycle. Arm PIE: 85 mg/m2 orally (divided into 2 doses, 12 hours apart) on day 3 and 10 of each cycle.<br>* Other names: NSC # 141540;Drug: Irinotecan<br>* 50 mg/m2 IV over 90 minutes on days 1 and 8 of each cycle (Arm PIE only).<br>* Other names: CPT-11;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST) | Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR | Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of response is defined as the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started. | Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry. | 
| Overall Survival | Overall survival is defined as the time from randomization to death. | Assessed every 3 months for 2 years, then every 6 months for 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extensive stage small cell lung cancer, Topotecan, Etoposide, Cisplatin, Irinotecan