Irinotecan and Carboplatin as First-Line Therapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: The general results of combining irinotecan and platin-based chemotherapies have been very encouraging. As the toxicity profile associated with carboplatin is preferable over cisplatin it is our expectation that patients and physicians would prefer to use this combination if it is equally or more efficacious. To date there has been no agreement regarding the optimal combination of these agents. Based on the trials described in the protocol and our experience with carboplatin/irinotecan in the treatment of non-small cell lung cancer the present trial will utilize a 21-day cycle of irinotecan 50 mg/m2 given on days 1 and 8 and carboplatin AUC 5 (based on the Calvert formula) on day 1. PURPOSE: This phase II trial is studying how well giving irinotecan together with carboplatin works as first-line therapy in treating patients with extensive-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary To examine the anti-tumor efficacy of the combination of Irinotecan (CPT-11) and Carboplatin as first-line therapy as assessed by response rate in patients with chemo-naïve extensive stage small cell lung cancer. Secondary Determine the safety, tolerability, and feasibility of this regimen in these patients. Determine the time to progression in patients treated with this regimen. Determine the overall survival of patients treated with this regimen. OUTLINE: This is a multicenter, open-label study. Patients receive irinotecan IV over 30-90 minutes on days 1 and 8 and carboplatin IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 2 months. PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

Official Title
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A Phase II Trial of Carboplatin and Irinotecan (CPT-11) as First-Line Therapy for Patients With Extensive Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed small cell lung cancer (SCLC) Extensive stage small cell lung cancer Must have ≥ 1 unidimensionally measurable lesion (longest diameter to be recorded) ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Lesion cannot be from a previously irradiated area Lesions that are considered nonmeasurable include the following: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Tumor lesions in a previously irradiated area No brain metastasis or carcinomatous meningitis unless stable and asymptomatic PATIENT CHARACTERISTICS ECOG performance status 0-2 Life expectancy ≥ 3 months ANC ≥ 1,500/mm³ Platelet count > 100,000/mm³ Serum bilirubin ≤ 1.5 mg/dL AST/SGOT ≤ 2.5 times upper limit of normal (ULN) (or ≤ 5 times ULN if liver metastases present) Serum creatinine ≤ 2.0 mg/dl Hemoglobin ≥ 9.0 g/dl Exclusion Criteria: CNS metastasis excluded unless: stable and asymptomatic Coexisting medical condition that would preclude study compliance Patients with Gilbert's disease Uncontrolled diabetes mellitus, defined as random blood sugar ≥ 300 mg/dl or > 16.6 mmol/L Patients who do not discontinue phenytoin, phenobarbitol, carbamazipine, or other enzyme-inducing anticonvulsant drugs at least 7 days prior to first treatment dose on study. Gabapentin is permitted Patients who do not discontinue St. John's Wort prior to first treatment dose on study. Patients who are pregnant or breast feeding Concomitant second active malignancy except for any in situ cancer or adequately treated basal cell or squamous cell skin cancer or any cancer from which the patients has been disease-free for at least 2 years No administration of any prior systemic anticancer therapy for extensive stage SCLC such as: chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, or other experimental agents. Concurrent use of other anticancer therapy including inhibitors of vascular endothelial or epidermal growth factor pathways is prohibited. Prior radiation is allowed Symptomatic brain metastasis or carcinomatous meningitis PRIOR CONCURRENT THERAPY:

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Intervention<br>Lung cancer patients will be treated for four 3-week cycles (12 weeks) in the absence of progressive disease, unacceptable toxicity, or withdrawal of patient consent. Up to two additional cycles may be administered at the discretion of the treating physician. If at treatment withdrawal the disease has responded or is stable, the patient will continue to be followed for efficacy (i.e. until progressive disease)at 8 week intervals. Following the diagnosis of progressive disease, patients will be followed every two months for survival. | Drug: Carboplatin<br>* Carboplatin dosage calculation to be given on day 1, every 21 days: Carboplatin (mg) = (AUC of 5) x (GFR + 25) *up to 6 cycles at physician's discretion<br>* Other names: Paraplatin;Drug: irinotecan hydrochloride<br>* 50 mg/m2 IV on days 1 and 8 every 21 days Should be infused IV over 30- 90 minutes.<br>* Other names: CPT-11;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Response | Patient response to treatment: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started Complete response (CR): disappearance of all target lesions Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD | 1.66 months (average duration, on treatment date to best response date) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events | Number of participants with adverse events, according to grade of event, using the NCI Common Toxicity Criteria (version 2.0) grading system to assign a grade to each event | date off treatment or progression of disease, up to 18 weeks | 
| Time to Progression | Time to progression in months | 9.9 months (on study date to progression) | 
| Overall Survival |  | On study date to death | 

 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