Surgery With or Without Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus

Esophageal Cancer Clinical Trial

Official title:

A Prospective Randomized Phase III Trial Comparing Trimodality Therapy (Cisplatin, 5-FU, Radiotherapy, and Surgery) to Surgery Alone for Esophageal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003118
• Other study ID #: CALGB-9781
• Secondary ID: U10CA031946CLB-C
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: July 1, 2016
• Start date: October 1997
• Est. completion date: March 2000

Study information

• Verified date: June 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether surgery is more effective with or without chemotherapy and radiation therapy for cancer of the esophagus.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy and radiation therapy in treating patients who have cancer of the esophagus that can be surgically removed.

Description:

OBJECTIVES: I. Compare overall five-year survival rates and treatment failures in patients receiving neoadjuvant cisplatin (CDDP) plus fluorouracil (5-FU) with concomitant radiotherapy followed by surgical resection versus patients receiving surgery alone. II. Assess and compare the toxicities of each approach. III. Compare the incidence and pattern of local (gastric or esophageal bed or regional lymph nodes) and distant (supraclavicular lymph node, liver, peritoneal carcinomatosis, or lung, brain, etc.) recurrence. IV. Evaluate the prognostic ability of noninvasive and minimally invasive pretreatment staging with regard to survival and recurrence. V. Evaluate the ability of preresection adjuvant chemotherapy with concomitant radiation therapy to render tumors to lower stages. VI. Evaluate the impact of lymph nodes on survival and recurrence.

OUTLINE: This a two arm, randomized study. Patients are stratified by: cell type of cancer (squamous cell vs adenocarcinoma); lymph nodes (positive vs negative); and stage (invasive vs noninvasive). Patients in arm I undergo chemotherapy and radiotherapy within 24 hours of each other. Chemotherapy consists of cisplatin (CDDP) by bolus IV infusion over 30 minutes on day 1 and again on day 29. Fluorouracil (5-FU) is administered by continuous IV infusion for 4 days (on days 1-4 and 29-32) after completion of cisplatin. Radiotherapy is administered on days 1-5, 8-12, 15-19, 22-26, and 29-33, with a boost on days 36-38. If there is no disease progression or unresectable disease, surgery is performed within 3-8 weeks following completion of therapy. Patients in arm II undergo surgery alone no later than 6 weeks postrandomization. Patients are followed at least every 3 months for two years, then every 6 months for the next two years, and annually thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: March 2000
• Est. primary completion date: March 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

1. Patients with histologically documented untreated squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastro-esophageal junction and with less than 2 cm distal spread into the gastric cardia were eligible.

2. No evidence of distant metastatic disease by history and physical examination

3. Upper endoscopy with biopsy, computed tomography (CT) of the chest and upper abdomen, and pulmonary function studies are required.

4. Bone scan is required for alkaline phosphatase more than 3X the institutional normal value.

5. Bronchoscopy is required if the primary tumor was adjacent to the trachea or left main stem bronchus.

6. Patients are required to have:

• granulocyte counts =1,800/mL

• platelet count = 100,000/mL

• creatinine clearance = 50 mL/min

7. Esophageal ultrasound (EUS) and preresection staging by thoracoscopy (ts) and laparoscopy/minilaparotomy (ls), including biopsy of celiac axis and lesser curvature are recommended

8. Tumors must be considered surgically resectable (T1-3, NX), including regional thoracic lymph node (N1) metastases.

9. Patients with supraclavicular lymph nodes measuring = 1.5 cm by CT (not palpable) are eligible.

10. Patients with lymph node metastases to levels 15 to 20 (predominantly celiac axis and paracardial nodes) =1.5 cm by CT.

11. Patients may not have previously received chemotherapy or radiation therapy for this tumor or any radiation therapy that would overlap the radiation fields required for this malignancy.

12. Patients with previous malignancies are eligible if more than 5 years had elapsed from diagnosis without evidence of tumor recurrence.

13. There can be no other serious illness that would limit survival to less than 2 years, or psychiatric condition that would prevent compliance with treatment or informed consent. Patients with uncontrolled or severe cardio- vascular disease,pulmonary disease, oractive infections are excluded.

14. Pregnant patients are excluded.

15. Informed consent is required for all patients.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• cisplatin

• fluorouracil

Procedure:
• surgical procedure

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	University of Illinois at Chicago Health Sciences Center	Chicago	Illinois
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of California San Diego Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	North Shore University Hospital	Manhasset	New York
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County	Mount Holly	New Jersey
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	University of Rochester Cancer Center	Rochester	New York
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Krasna M, Tepper JE, Niedzwiecki D, et al.: Trimodality therapy is superior to surgery alone in esophageal cancer: results of CALGB 9781. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Fra

Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: — View Citation

Tepper JE, Krasna M, Niedzwiecki D, et al.: Superiority of trimodality therapy to surgery alone in esophageal cancer: results of CALGB 9781. [Abstract] J Clin Oncol 24 (Suppl 18): A-4012, 2006.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		up to 5 years	No