Clinical trial NCT00009880: Combination Chemotherapy Plus Radiation Therapy With or Without Fluorouracil in Treating Patients With Cancer of the Esophagus or Stomach
Official title: Non-Operative Therapy Of Local-Regional Carcinoma Of The Esophagus: A Randomizd Phase II Study Of Two Paclitaxel-Based Chemoradiotherapy Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: stage I gastric cancer
stage II gastric cancer
stage III gastric cancer
stage I esophageal cancer
stage II esophageal cancer
stage III esophageal cancer
adenocarcinoma of the stomach
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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. Combining chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combination chemotherapy plus radiation therapy with and without fluorouracil in treating patients who have cancer of the esophagus or stomach.

Detailed description: OBJECTIVES:

* Compare the survival and failure patterns in patients with previously untreated carcinoma of the esophagus or gastroesophageal junction treated with cisplatin, paclitaxel, and concurrent radiotherapy with or without fluorouracil.
* Compare the tolerance of these regimens by these patients.
* Compare the overall quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to percentage of weight loss (less than 10% vs 10% or more), disease histology (adenocarcinoma vs squamous cell carcinoma), and lesion size (no more than 5 cm vs more than 5 cm). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive induction chemotherapy comprising fluorouracil IV continuously over 24 hours and cisplatin IV over 1 hour on days 1-5, paclitaxel IV continuously over 24 hours on day 1, and filgrastim (G-CSF) subcutaneously daily on days 6-15. Treatment repeats every 4 weeks for up to 2 courses. Patients with stable or responsive disease after the first course of induction therapy receive a second course of therapy. Patients with local disease progression after the first course proceed to chemoradiotherapy.

Beginning on day 29 of the last course of induction chemotherapy, patients undergo radiotherapy 5 days a week for 5.5 weeks. Patients also receive fluorouracil IV continuously over 24 hours on days 1-5, 8-12, 15-19, 22-26, and 29-33, and paclitaxel IV over 3 hours on days 1, 8, 15, 22, and 29.

* Arm II: Patients receive induction chemotherapy comprising cisplatin IV and paclitaxel IV over 3 hours on day 1. Treatment continues every 3 weeks for 2 courses as in arm I.

Beginning on day 29 of the last course of induction chemotherapy, patients undergo radiotherapy as in arm I. Patients also receive cisplatin IV on days 1, 8, 15, 22, 29, and 36, and paclitaxel IV continuously over 96 hours on days 1-4, 8-11, 15-18, 22-25, 29-32, and 36-39.

Quality of life is assessed at baseline, within 1 week after radiotherapy, at 6 weeks after study completion, every 4 months for 1 year, every 6 months for 2 years, and then annually for 5 years.

Patients are followed within 8 weeks, every 4 months for 1 year, every 6 months for two years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients (42 per treatment arm) will be accrued for this study within 21 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

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

  * Stage I-III (T1, N1, M0; T2-4, N any, M0)

    * Supraclavicular or celiac lymph node involvement allowed
* Disease entirely confined to the esophagus or gastroesophageal junction and peri-esophageal soft tissue
* Cervical esophageal carcinoma allowed
* No tumor extension beyond 2 cm into stomach
* No multiple primary carcinomas of the esophagus
* No evidence of disseminated cancer
* No tracheoesophageal fistula or direct invasion into the mucosa of the trachea or major bronchi

  * Bronchoscopy with biopsy and cytology required if the primary carcinoma is less than 26 cm from the incisors or is at or above the carina by imaging study

PATIENT CHARACTERISTICS:

Age:

* Not specified

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil 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
* Creatinine clearance at least 65 mL/min

Cardiovascular:

* No uncontrolled heart disease
* No uncontrolled hypertension

Other:

* Total oral/enteral intake must be at least 1,700 kCal/day
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No uncontrolled diabetes
* No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior systemic chemotherapy
* No other concurrent chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior chest radiotherapy

Surgery:

* No prior major esophageal surgery

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Foundation for Cancer Research and Education
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Northridge
country: United States
facility: Leavey Cancer Center at Northridge Hospital Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Muncie
country: United States
facility: Cancer Center at Ball Memorial Hospital
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Terre Haute
country: United States
facility: Union Hospital
state: Indiana
city: Dubuque
country: United States
facility: Wendt Regional Cancer Center at Finley Hospital
state: Iowa
city: Edgewood
country: United States
facility: Esther Marie Hatton Cancer Care Center at St. Elizabeth Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: Tulane Cancer Center at Tulane University Hospital and Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Omaha
country: United States
facility: Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
state: Nebraska
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Pomona
country: United States
facility: Atlantic City Medical Center - Mainland Division
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: East Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Akron
country: United States
facility: Akron General's McDowell Cancer Center
state: Ohio
city: Akron
country: United States
facility: Akron City Hospital at Summa Health System
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel West Hospital
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Delaware
country: United States
facility: Grady Memorial Hospital
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Marietta
country: United States
facility: Strecker Cancer Center at Marietta Memorial Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Cancer Care Program at Licking Memorial Hospital
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital Cancer Center
state: Pennsylvania
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: East Stroudsburg
country: United States
facility: Dale and Frances Hughes Cancer Center at Pocono Medical Center
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center at 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: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Mercy Hospital of Pittsburgh
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Reading
country: United States
facility: Reading Hospital and Medical 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: 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
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at All Saints Healthcare
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jaffer A. Ajani, MD
role: STUDY_CHAIR
References:
citation: Ajani JA, Winter K, Komaki R, Kelsen DP, Minsky BD, Liao Z, Bradley J, Fromm M, Hornback D, Willett CG. Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113. J Clin Oncol. 2008 Oct 1;26(28):4551-6. doi: 10.1200/JCO.2008.16.6918. Epub 2008 Jun 23.
citation: Komaki R, Winter K, Ajani J: Non-operative therapy of local-regional carcinoma of the esophagus: a randomized phase II study of two paclitaxel-based chemoradiotherapy regimens (RTOG 0113). [Abstract] The American Radium Society 89th Annual Meeting, May 5-29, 2007, Amsterdam, Netherlands. A-SS-2, 1, 2007.
citation: Komaki R, Winter K, Ajani A, et al.: A randomized phase II study of two paclitaxel-based chemoradiotherapy regimens for patients with the non-operative esophageal carcinoma (RTOG 0113). [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-142, S79-80, 2006.