Combination Chemotherapy Followed By Chemoradiotherapy, With or Without Surgery, in Treating Patients With Resectable Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

A Phase II Study Of Paclitaxel-Based Chemoradiotherapy Regimen With Selective Surgical Salvage For Resectable Locoregionally Advanced Carcinoma Of The Esophagus

RATIONALE: Drugs used in chemotherapy such as paclitaxel, fluorouracil, and cisplatin 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. Combining chemotherapy with radiation therapy may kill more tumor cells

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by chemoradiotherapy, with or without surgery, works in treating patients with resectable locally advanced cancer of the esophagus or gastroesophageal junction.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Biological: filgrastim; Biological: pegfilgrastim; Drug: cisplatin; Drug: fluorouracil; Drug: paclitaxel; Procedure: conventional surgery; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

• Determine the feasibility of treatment with paclitaxel, cisplatin, and fluorouracil followed by chemoradiotherapy and possible surgical salvage in patients with resectable locally advanced carcinoma of the esophagus or gastroesophageal junction.
• Determine the overall and disease-free survival of patients treated with this regimen.
• Determine the treatment-related toxicity of this regimen in these patients.
• Determine the tolerance to surgical salvage in patients treated with this regimen.
• Determine the morbidity and mortality of surgical salvage in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive fluorouracil (5-FU) IV continuously over 96 hours beginning on days 1 and 29; cisplatin IV over 1 hour on days 1-5 and 29-33; paclitaxel IV over 2 hours on days 1 and 29; and pegfilgrastim subcutaneously (SC) on days 6 and 34 OR filgrastim (G-CSF) SC on days 6-15 and 34-42. Treatment continues in the absence of unacceptable toxicity.
• Chemoradiotherapy: Patients receive cisplatin IV over 1 hour on days 57-61 and 5-FU IV continuously on days 57-61, 64-68, 71-75, 78-82, 85-89, and 92-96. Patients concurrently undergo external beam radiotherapy on days 57-61, 64-68, 71-75, 78-82, 85-89, and 92-96.

Patients with residual or recurrent esophageal disease 4-6 weeks after completion of chemoradiotherapy may undergo salvage esophagectomy.

Patients are followed periodically.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study within 18 months.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Mission Hills, California, United States, 91346-9600
      • Providence Holy Cross Cancer Center
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Summit Medical Center
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • San Pablo, California, United States, 94806
      • J.C. Robinson, M.D. Regional Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Hospital of Saint Raphael
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
    • Panama City, Florida, United States, 32405
      • Gulf Coast Cancer Treatment Center
  • Georgia
    • Savannah, Georgia, United States, 31403-3089
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60608
      • Mount Sinai Hospital Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center at Finley Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 708169990
      • Ochsner Clinic of Baton Rouge
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48106-0995
      • St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology, Limited - Escanaba
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Iron Mountain, Michigan, United States, 49801
      • Green Bay Oncology, Limited - Iron Mountain
    • Jackson, Michigan, United States, 49201
      • Foote Hospital
    • Lansing, Michigan, United States, 48909
      • Sparrow Regional Cancer Center
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • St. Louis Park, Minnesota, United States, 55416
      • Park Nicollet Health Services
    • St. Paul, Minnesota, United States, 55102
      • United Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic, P.A.
  • Missouri
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program - Marlton
    • Red Bank, New Jersey, United States, 07701
      • Booker Cancer Center at Riverview Medical Center
    • Toms River, New Jersey, United States, 08755
      • Community Regional Cancer Center at Community Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Research and Treatment Center
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Regional Medical Center at Lovelace Sandia Health System
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY downstate Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Wilson, North Carolina, United States, 27893
      • Wilmed Radiation Oncology Services
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Akron City Hospital
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Regional Cancer Center at Delaware County Memorial Hospital
    • Paoli, Pennsylvania, United States, 19301-1792
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Rose Ramer Cancer Clinic at Anderson Area Medical Center
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Schiffler Cancer Center at Wheeling Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology, Limited - Oconto Falls
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology, Limited - Sturgeon Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction

  • Primary (non-recurrent) disease
  • Amenable to resection
  • Stage greater than T1, N0 by endoscopic ultrasound
  • Must be entirely confined to the esophagus or gastroesophageal junction and periesophageal soft tissue
  • Tumor may not extend more than 2 cm into the stomach
• No multiple primary carcinomas of the esophagus
• No cervical esophageal carcinoma or tumors less than 5 cm from cricopharyngeus

• No evidence of disseminated cancer

  • Suggestion of liver metastases by positron emission tomography must be proven negative by biopsy or other imaging studies
  • Palpable supraclavicular nodes must be negative for cancer by biopsy
• Bronchoscopy required for lesions less than 26 cm from the incisors to exclude tracheoesophageal fistula or invasion
• No celiac adenopathy greater than 2 cm

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• Not specified

Renal

• Creatinine no greater than 1.5 mg/dL AND/OR
• Creatinine clearance at least 65 mL/min
• Calcium no greater than 11 mg/dL

Cardiovascular

• No uncontrolled heart disease
• No uncontrolled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to comprehend study requirements and considered likely to comply with study parameters
• No other malignancy within the past 5 years except curable nonmelanoma skin cancer or carcinoma in situ of the cervix
• No uncontrolled diabetes
• No hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 5 years since prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior chest or upper abdomen radiotherapy

Surgery

• No prior esophageal or gastric surgery

Other

• No concurrent photodynamic therapy
• No other concurrent investigational agents for esophageal carcinoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ChemoRT and selective surgery; Induction therapy of fluorouracil, cisplatin, paclitaxel, and pegfilgrastim OR filgrastim, then chemoradiotherapy of concurrent cisplatin and fluorouracil with external beam radiotherapy (RT), followed by selective salvage therapy.

Biological: filgrastim; During induction therapy, patients ≤ 70 kg will receive 300 μg OR patients >70 kg will receive 480 μg subcutaneously on days 6-15 and 34-42.; Other Names: G-CSF; Biological: pegfilgrastim; During induction therapy, patients receive 6 mg subcutaneously on days 6 and 34.; Other Names: PEG-G-CSF; Drug: cisplatin; During induction therapy, patients receive 15 mg/m^2/day by IV over 1 hour on days 1-5 and 29-33. During radiotherapy, patients receive 15 mg/m^2/day by IV over 1 hour beginning on days 57-61.; Drug: fluorouracil; During induction therapy, patients receive 650 mg/m^2/day by IV continuously over 96 hours beginning on days 1 and 29. During radiotherapy, patients receive 300 mg/m^2/day by IV continuously over 96 hours beginning on day 57 for 5 cycles.; Other Names: 5-FU; Drug: paclitaxel; During induction therapy, patients receive 200 mg/m^2/day by IV over 2 hours on days 1 and 29.; Procedure: conventional surgery; Patients with residual or recurrent esophageal disease 4-6 weeks after completion of chemoradiotherapy may undergo salvage esophagectomy.; Radiation: radiation therapy; External beam radiotherapy with megavoltage linear accelerators (> 6 MV) will be used to deliver multiple (> 2) field techniques. Patients will be treated 5 days/week at 1.8 Gy/day for 28 days for a total dose of 50.4 Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (1-year Rate Reported)	One-year survival estimate is reported. Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact. This analysis was planned to occur when all patients had been potentially followed for 1 year. On the basis of a 1-year survival rate of 60% from the Radiation Therapy Oncology Group (RTOG) esophageal database, 38 analyzable patients with a 1-year survival rate of 77.5% or better was needed for this trial to be deemed promising enough for development of a Phase III protocol (type I error of 0.05 and type II error of 0.20).	From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 1 year.

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequency of Major (Grade 4) Acute Treatment-related Toxicities	From start of chemotherapy to surgery or 2 months after chemoradiation (for patients not undergoing surgery).
Frequency of Patients With Persistent or Recurrent Disease Eligible for Surgical Salvage Resection	Analysis occurs with the primary outcome measure.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Study Chair: Stephen G. Swisher, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Swisher SG, Winter KA, Komaki RU, Ajani JA, Wu TT, Hofstetter WL, Konski AA, Willett CG. A Phase II study of a paclitaxel-based chemoradiation regimen with selective surgical salvage for resectable locoregionally advanced esophageal cancer: initial reporting of RTOG 0246. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1967-72. doi: 10.1016/j.ijrobp.2011.01.043. Epub 2011 Apr 18.

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (Estimate): October 7, 2003

Study Record Updates

• Last Update Posted (Actual): February 17, 2017
• Last Update Submitted That Met QC Criteria: December 30, 2016
• Last Verified: December 1, 2016

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
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Adjuvants, Immunologic; Paclitaxel; Fluorouracil; Lenograstim
• Other Study ID Numbers: RTOG-0246; CDR0000306455