Oblimersen, Cisplatin, and Fluorouracil in Treating Patients With Advanced Esophageal, Gastroesophageal Junction, or Stomach Cancer

Condition(s) targeted: Esophageal Cancer; Gastric Cancer

Intervention: cisplatin (Drug); fluorouracil (Drug); oblimersen (Drug); antisense therapy (Procedure); chemosensitization/potentiation therapy (Procedure); chemotherapy (Procedure)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: Albert Einstein College of Medicine of Yeshiva University

Official(s) and/or principal investigator(s):
Andreas Kaubisch, MD, Study Chair, Affiliation: Albert Einstein College of Medicine of Yeshiva University

RATIONALE: Drugs used in chemotherapy such as cisplatin and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. PURPOSE: This phase I/II trial is studying the side effects and best dose of oblimersen when given with cisplatin and fluorouracil and to see how well they work in treating patients with locally advanced, recurrent, or metastatic cancer of the esophagus, gastroesophageal junction, or stomach.

Official title: A Phase I/II Study of Genasense (G3139) in Combination With Cisplatin and Fluorouracil in Patients With Advanced Esophageal, Gastro-Esophageal Junction and Gastric Cancer

Study design: Treatment

Primary outcome:

Analysis of biopsy specimens

Drug effect as measured by changes in microarray expression patterns

Secondary outcome: Patterns of gene expression pre- and post-treatment

Detailed description: OBJECTIVES: Determine the maximum tolerated dose of oblimersen administered with cisplatin and fluorouracil in patients with advanced esophageal, gastroesophageal junction, or gastric cancer. Determine the toxic effects of this regimen in these patients. OUTLINE: This is a pilot, multicenter, dose-escalation study of oblimersen. Phase I: Patients receive oblimersen IV continuously on days 1-7, fluorouracil IV continuously on days 4-8, and cisplatin IV on day 4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oblimersen 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. An additional 12 patients are treated at the MTD. Phase II: Patients receive treatment as in phase I with oblimersen at the MTD. PROJECTED ACCRUAL: Approximately 37-97 patients (3-36 for phase I and 34-67 for phase II) will be accrued for this study within 15-18 months.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the esophagus, gastroesophageal junction, or stomach Squamous cell carcinoma of the esophagus also eligible Locally advanced, recurrent, or metastatic disease not amenable to complete surgical resection or definitive radiotherapy Clinically evaluable disease Measurable disease or clinically evaluable disease Patients with inaccessible tumor tissue must have at least 1 measurable tumor deposit No known brain metastases PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy More than 12 weeks Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin normal AST and ALT no greater than 2. 5 times upper limit of normal Renal Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No prior allergic reaction attributed to compounds of similar chemical or biological composition to antisense oligonucleotides, cisplatin, fluorouracil, or other study agents No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance Willing to undergo 2 biopsies (for patients with accessible tumor only, defined as tumors reachable by esophagogastroduodenoscopy OR metastases which can be biopsied with commonly utilized methods [e. g., CT-guided biopsy]) PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent growth factors during the first course of study therapy Chemotherapy No more than 1 prior chemotherapy regimen for advanced, recurrent, or metastatic disease Prior significant full-dose chemotherapy (at least 2 months of therapy) during primary treatment is considered a prior regimen of chemotherapy (unless at least 6 months have elapsed since completion of treatment) An additional chemotherapy regimen allowed for recurrent or progressive disease more than 6 months after the completion of prior significant chemotherapy At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Endocrine therapy Not specified Radiotherapy See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered Surgery Prior surgery allowed Other More than 4 weeks since prior photodynamic therapy No prior oblimersen No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients Concurrent photodynamic therapy for obstruction untreatable by stent, laser, or dilation allowed

Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States

Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States

Mount Sinai Medical Center, New York, New York 10029, United States

New York Weill Cornell Cancer Center at Cornell University, New York, New York 10021, United States

North Shore University Hospital, Manhasset, New York 11030, United States

NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2003
Last updated: December 25, 2007