Celecoxib, Paclitaxel, and Carboplatin in Treating Patients With Cancer of the Esophagus

A Phase II Study Of Preoperative Celecoxib/Paclitaxel/Carboplatin For Squamous Cell And Adenocarcinoma Of The Esophagus

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may increase the effectiveness of a chemotherapy drug by making tumor cells more sensitive to the drug. Celecoxib may also stop the growth of tumor cells by stopping blood flow to the tumor and/or may block the enzymes necessary for their growth. Combining celecoxib with paclitaxel and carboplatin before surgery may shrink the tumor so that it can be removed during surgery. Giving celecoxib alone after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving celecoxib together with paclitaxel and carboplatin works in treating patients who are undergoing surgery for esophageal cancer.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: celecoxib; Drug: paclitaxel; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy

Detailed Description

OBJECTIVES:

Primary

• Determine the rate of complete pathological response and/or minimal residual microscopic disease in patients with squamous cell or adenocarcinoma of the esophagus treated with preoperative celecoxib, paclitaxel, and carboplatin.

Secondary

• Determine the clinical response rate of patients treated with this regimen.
• Determine the chemotherapy-related toxicity of this regimen in these patients.
• Determine the time to progression, disease-free survival, and overall survival of patients treated with this regimen.

OUTLINE: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on days 1, 22, and 43. Patients also receive oral celecoxib twice daily beginning 3-7 days before the first dose of chemotherapy and continuing until the morning of planned surgical resection (between days 64 and 71). Approximately 28-56 days after resection, patients may resume oral celecoxib twice daily and continue for 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed periodically for 18 months after surgery.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study within 18 months.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

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

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

DISEASE CHARACTERISTICS:

• Histologically confirmed esophageal cancer of 1 of the following cellular types:

  • Squamous cell
  • Adenocarcinoma
• Potentially resectable disease
• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• No bleeding disorder

Hepatic

• Bilirubin normal
• AST and ALT less than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No significant history of unstable cardiovascular disease
• No inadequately controlled hypertension
• No angina
• No myocardial infarction within the past 6 months
• No ventricular cardiac arrhythmias requiring medication
• No congestive heart failure that would preclude study therapy

Pulmonary

• Pulmonary function acceptable for surgery
• No interstitial pneumonia
• No interstitial fibrosis

Gastrointestinal

• No history of peptic ulcer disease
• No irritable bowel syndrome
• No inflammatory bowel disease
• No chronic diarrhea
• No bowel obstruction within the past 5 years

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity or allergic reactions to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
• No hypersensitivity to paclitaxel or carboplatin
• No other serious underlying medical condition that would preclude study therapy
• No significant psychiatric illness that would preclude study compliance
• No uncontrolled diabetes mellitus
• No uncontrolled infection
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• No concurrent chronic steroid use except inhaled mometasone or fluticasone

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 3 weeks since other prior clinical trial therapy
• At least 72 hours since prior nonsteroidal anti-inflammatory drugs (NSAIDs)
• No concurrent chronic NSAID use (7 or more days of continuous therapy per month OR 3 or more days of therapy per week)
• No other concurrent investigational agents
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin or phenobarbital)
• No other concurrent cyclo-oxygenase (COX)-2 inhibitors
• No concurrent lithium or fluconazole
• Concurrent low-dose aspirin (325 mg/day or less) allowed for cardiovascular prophylaxis

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological response rate at time of surgical resection	At completion of pathology report.

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical response rate	At the time of tumor assessment obtained prior to definitive surgery approximately 1-2 weeks prior to surgical resection.
Disease-free survival	From start of treatment to time of recurrent disease measured postoperatively every 6 months for 18 months.
Overall survival	18 months after surgery
Toxicities and safety	30 days after completion of study treatment.

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Pfizer
• Investigators: Study Chair: Nasser K. Altorki, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): December 8, 2009
• Last Update Submitted That Met QC Criteria: December 7, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: stage II esophageal cancer; stage III esophageal cancer; squamous cell carcinoma of the esophagus; adenocarcinoma of the esophagus; stage I esophageal cancer; stage IV esophageal cancer (lymph node metastasis only)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Cyclooxygenase 2 Inhibitors; Carboplatin; Paclitaxel; Celecoxib
• Other Study ID Numbers: CDR0000316464; NYWCCC-0902-463