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

NCT ID: NCT00003118

Last Updated: 2016-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-10-31
• Study Completion Date: 2000-03-31

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.

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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy + Radiation + Surgery

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

surgical procedure

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Surgery

Group Type: ACTIVE_COMPARATOR

surgical procedure

Intervention Type: PROCEDURE

Interventions

cisplatin

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

surgical procedure

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Krasna, MD

Role: STUDY_CHAIR

Jersey Shore University Medical Center

Locations

University of California San Diego Cancer Center

La Jolla, California, United States

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Barnes-Jewish Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Fox Chase Cancer Center at Virtua-Memorial Hospital Burlington County

Mount Holly, New Jersey, United States

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

CCOP - North Shore University Hospital

Manhasset, New York, United States

North Shore University Hospital

Manhasset, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Mount Sinai Medical Center, NY

New York, New York, United States

University of Rochester Cancer Center

Rochester, New York, 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

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, 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

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Vermont Cancer Center

Burlington, Vermont, United States

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

References

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: CALGB 9781. J Clin Oncol. 2008 Mar 1;26(7):1086-92. doi: 10.1200/JCO.2007.12.9593.

Reference Type: RESULT

PMID: 18309943 (View on PubMed)

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 Francisco, California. A-4, 2006.

Reference Type: RESULT

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.

Reference Type: RESULT

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CLB-C9781

Identifier Type: -

Identifier Source: secondary_id

E-C9781

Identifier Type: -

Identifier Source: secondary_id

NCCTG-C9781

Identifier Type: -

Identifier Source: secondary_id

RTOG-9716

Identifier Type: -

Identifier Source: secondary_id

CDR0000065873

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-9781

Identifier Type: -

Identifier Source: org_study_id