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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Extensive Stage Small Cell Lung Cancer	Biological: oblimersen sodium; Drug: carboplatin; Drug: etoposide; Other: pharmacological study; Other: laboratory biomarker analysis	Phase 1

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	12 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I Study Of Genasense, A Bcl-2 Antisense Oligonucleotide, Combined With Carboplatin And Etoposide In Patients With Small Cell Lung Cancer
Study Start Date :	April 2001
Actual Primary Completion Date :	January 2004

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Treatment (oblimersen sodium, carboplatin, etoposide); 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; Given IV; Other Names: augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplat; Paraplatin Drug: etoposide; Given IV; Other Names: EPEG; VP-16; VP-16-213 Other: pharmacological study; Correlative studies; Other Name: pharmacological studies Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

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Primary Outcome Measures :

1. Feasibility and toxicity of the regimen monitored using the Common Toxicity Criteria Version 2.0 [ Time Frame: Up to 3 years ]
   Data will be summarized separately for each dose level, by severity, and type of toxicity.
2. Maximally tolerated dose of oblimersen sodium [ Time Frame: 8 days ]

Secondary Outcome Measures :

1. Potential antitumor activity (responses to therapy) [ Time Frame: Up to 3 years ]
   Will be analyzed using simple descriptive statistics only.
2. Whether concomitant carboplatin and etoposide administration alters oblimersen sodium steady state level [ Time Frame: Day 6 and 8 ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Charles Rudin	University of Chicago Comprehensive Cancer Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00017251 History of Changes
Other Study ID Numbers:	NCI-2012-02387; 10992A; N01CM17102 ( U.S. NIH Grant/Contract ); CDR0000068667 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted:	January 27, 2003
Last Update Posted:	January 24, 2013
Last Verified:	January 2013

Additional relevant MeSH terms:

Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms	Etoposide phosphate; Oblimersen; Carboplatin; Etoposide; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action