A Phase I Study Of Genasense, A Bcl-2 Antisense Oligonucleotide, Combined With Carboplatin And Etoposide In Patients With 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
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.
Inclusion Criteria:
Histologically or cytologically confirmed extensive stage small cell lungcancer
No active CNS disease
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