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

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

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

Study Overview

• Status: Completed
• Conditions: Extensive Stage Small Cell Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: oblimersen sodium; Other: pharmacological study; Drug: etoposide; Drug: carboplatin

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles Rudin, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): January 1, 2004

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide; Etoposide phosphate; Oblimersen
• Other Study ID Numbers: NCI-2012-02387; N01CM17102 (U.S. NIH Grant/Contract); 10992A; CDR0000068667 (Registry Identifier: PDQ (Physician Data Query))