Clinical trial NCT00069953: Combination Chemotherapy Followed By Chemoradiotherapy, With or Without Surgery, in Treating Patients With Resectable Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction
Official title: A Phase II Study Of Paclitaxel-Based Chemoradiotherapy Regimen With Selective Surgical Salvage For Resectable Locoregionally Advanced Carcinoma Of The Esophagus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2003-10-07
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (1-year Rate Reported)
timeFrame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 1 year.
Secondary outcomes:
measure: Frequency of Major (Grade 4) Acute Treatment-related Toxicities
timeFrame: From start of chemotherapy to surgery or 2 months after chemoradiation (for patients not undergoing surgery).
measure: Frequency of Patients With Persistent or Recurrent Disease Eligible for Surgical Salvage Resection
timeFrame: Analysis occurs with the primary outcome measure.
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Hayward
country: United States
facility: Saint Rose Hospital
state: California
city: Mission Hills
country: United States
facility: Providence Holy Cross Cancer Center
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Summit Medical Center
state: California
city: Pleasanton
country: United States
facility: Valley Care Medical Center
state: California
city: San Pablo
country: United States
facility: J.C. Robinson, M.D. Regional Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: New Haven
country: United States
facility: Hospital of Saint Raphael
state: Connecticut
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Panama City
country: United States
facility: Gulf Coast Cancer Treatment Center
state: Florida
city: Savannah
country: United States
facility: Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Mount Sinai Hospital Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Dubuque
country: United States
facility: Wendt Regional Cancer Center at Finley Hospital
state: Iowa
city: Baton Rouge
country: United States
facility: Ochsner Clinic of Baton Rouge
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology, Limited - Iron Mountain
state: Michigan
city: Jackson
country: United States
facility: Foote Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Medical Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Health Services
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, P.A.
state: Mississippi
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program - Marlton
state: New Jersey
city: Red Bank
country: United States
facility: Booker Cancer Center at Riverview Medical Center
state: New Jersey
city: Toms River
country: United States
facility: Community Regional Cancer Center at Community Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Regional Medical Center at Lovelace Sandia Health System
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research and Treatment Center
state: New Mexico
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Wilson
country: United States
facility: Wilmed Radiation Oncology Services
state: North Carolina
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: Rose Ramer Cancer Clinic at Anderson Area Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Houston
country: United States
facility: M.D. Anderson Cancer Center at University of Texas
state: Texas
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Wheeling
country: United States
facility: Schiffler Cancer Center at Wheeling Hospital
state: West Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Stephen G. Swisher, MD
role: STUDY_CHAIR
References:
citation: 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.