Combination Chemotherapy Plus Oblimersen in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may make tumor cells more sensitive to chemotherapy drugs. Phase I trial to study the effectiveness of combination chemotherapy and oblimersen in treating patients who have extensive-stage small cell lung cancer

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of oblimersen when combined with standard dose carboplatin and etoposide in patients with previously untreated extensive stage small cell lung cancer. II. Determine the toxicity and feasibility of this regimen in these patients. III. Determine potential antitumor activity of this regimen as assessed by objective response in these patients. OUTLINE: This is a multicenter, dose-escalation study of oblimersen (G3139). Patients receive G3139 IV continuously on days 1-8, carboplatin IV over 30 minutes on day 6, and etoposide IV over 1 hour on days 6-8. Treatment repeats every 3 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of G3139 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: Approximately 6-12 patients will be accrued for this study within 5 months.

Official Title
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A Phase I Study Of Genasense, A Bcl-2 Antisense Oligonucleotide, Combined With Carboplatin And Etoposide In Patients With Small Cell Lung Cancer

Conditions
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Extensive Stage Small Cell Lung Cancer

Intervention / Treatment
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* Biological: oblimersen sodium
* Drug: carboplatin
* Drug: etoposide
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed extensive stage small cell lungcancer No active CNS disease CNS metastasis allowed provided patient completed 1 course of CNS radiotherapy Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 2 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal (ULN) PT and PTT no greater than 1.5 times ULN Creatinine normal Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reactions to compounds of similar chemical or biologic composition to study agents No other uncontrolled concurrent illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance See Disease Characteristics At least 1 week since prior CNS radiotherapy and recovered No prior radiotherapy to more than 25% of skeleton No other prior anticancer therapy No other concurrent investigational agents No other concurrent anticancer therapy No concurrent anticoagulation therapy No concurrent combination antiretroviral therapy for HIV-positive patients

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: Treatment (oblimersen sodium, carboplatin, etoposide)<br>Patients receive G3139 IV continuously on days 1-8, carboplatin IV over 30 minutes on day 6, and etoposide IV over 1 hour on days 6-8. Treatment repeats every 3 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression. | Biological: oblimersen sodium<br>* Given IV<br>* Other names: Genasense;Drug: carboplatin<br>* Given IV<br>* Other names: Paraplatin;Drug: etoposide<br>* Given IV<br>* Other names: VP-16-213;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility and toxicity of the regimen monitored using the Common Toxicity Criteria Version 2.0 | Data will be summarized separately for each dose level, by severity, and type of toxicity. | Up to 3 years | 
| Maximally tolerated dose of oblimersen sodium |  | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Potential antitumor activity (responses to therapy) | Will be analyzed using simple descriptive statistics only. | Up to 3 years | 
| Whether concomitant carboplatin and etoposide administration alters oblimersen sodium steady state level | Will be analyzed using a paired t-test. If there are outliers or the distribution of changes in oblimersen sodium levels appears to be highly non-normal, the data will be analyzed using the Wilcoxon singed-rank test. | Day 6 and 8 |