Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

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.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Albert Einstein Cancer Center at Albert Einstein College of Medicine

Andreas Kaubisch

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00064259
Information obtained from ClinicalTrials.gov on January 02, 2012

Back to Top