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

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00003118

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: cisplatin Drug: fluorouracil Procedure: surgical procedure Radiation: radiation therapy	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 1997

Actual Primary Completion Date :

Mar 1, 2000

Actual Study Completion Date :

Mar 1, 2000

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy + Radiation + Surgery	Drug: cisplatin Drug: fluorouracil Procedure: surgical procedure Radiation: radiation therapy
Active Comparator: Surgery	Procedure: surgical procedure

Arm

Intervention/Treatment

Experimental: Chemotherapy + Radiation + Surgery

Drug: cisplatin

Drug: fluorouracil

Procedure: surgical procedure

Radiation: radiation therapy

Active Comparator: Surgery

Procedure: surgical procedure

Outcome Measures

Primary Outcome Measures

Overall survival [up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
No evidence of distant metastatic disease by history and physical examination
Upper endoscopy with biopsy, computed tomography (CT) of the chest and upper abdomen, and pulmonary function studies are required.
Bone scan is required for alkaline phosphatase more than 3X the institutional normal value.
Bronchoscopy is required if the primary tumor was adjacent to the trachea or left main stem bronchus.
Patients are required to have:

granulocyte counts ≥1,800/mL
platelet count ≥ 100,000/mL
creatinine clearance ≥ 50 mL/min

Esophageal ultrasound (EUS) and preresection staging by thoracoscopy (ts) and laparoscopy/minilaparotomy (ls), including biopsy of celiac axis and lesser curvature are recommended
Tumors must be considered surgically resectable (T1-3, NX), including regional thoracic lymph node (N1) metastases.
Patients with supraclavicular lymph nodes measuring ≤ 1.5 cm by CT (not palpable) are eligible.
Patients with lymph node metastases to levels 15 to 20 (predominantly celiac axis and paracardial nodes) ≤1.5 cm by CT.
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.
Patients with previous malignancies are eligible if more than 5 years had elapsed from diagnosis without evidence of tumor recurrence.
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.
Pregnant patients are excluded.
Informed consent is required for all patients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
2	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
3	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
4	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
5	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
6	University of Illinois at Chicago Health Sciences Center	Chicago	Illinois	United States	60612
7	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
8	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
9	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
10	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
11	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
12	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
13	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
14	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
15	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
16	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
17	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756
18	Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County	Mount Holly	New Jersey	United States	08060
19	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
20	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
21	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
22	North Shore University Hospital	Manhasset	New York	United States	11030
23	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
24	New York Presbyterian Hospital - Cornell Campus	New York	New York	United States	10021
25	Mount Sinai Medical Center, NY	New York	New York	United States	10029
26	University of Rochester Cancer Center	Rochester	New York	United States	14642
27	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13210
28	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
29	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
30	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
31	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
32	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
33	Hahnemann University Hospital	Philadelphia	Pennsylvania	United States	19102-1192
34	Rhode Island Hospital	Providence	Rhode Island	United States	02903
35	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
36	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee	United States	38103
37	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498
38	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037