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

Esophageal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00069953
• Other study ID #: RTOG-0246
• Secondary ID: CDR0000306455
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 3, 2003
• Last updated: November 14, 2015
• Start date: September 2003

Study information

• Verified date: November 2015
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 43
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

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.
• pegfilgrastim
During induction therapy, patients receive 6 mg subcutaneously on days 6 and 34.

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Akron City Hospital	Akron	Ohio
United States	Albuquerque Regional Medical Center at Lovelace Sandia Health System	Albuquerque	New Mexico
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Rose Ramer Cancer Clinic at Anderson Area Medical Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Ochsner Clinic of Baton Rouge	Baton Rouge	Louisiana
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Mount Sinai Hospital Medical Center	Chicago	Illinois
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hattiesburg Clinic, P.A.	Hattiesburg	Mississippi
United States	Saint Rose Hospital	Hayward	California
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Green Bay Oncology, Limited - Iron Mountain	Iron Mountain	Michigan
United States	Foote Hospital	Jackson	Michigan
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program - Marlton	Marlton	New Jersey
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Providence Holy Cross Cancer Center	Mission Hills	California
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Hospital of Saint Raphael	New Haven	Connecticut
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Summit Medical Center	Oakland	California
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Gulf Coast Cancer Treatment Center	Panama City	Florida
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Valley Care Medical Center	Pleasanton	California
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Booker Cancer Center at Riverview Medical Center	Red Bank	New Jersey
United States	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	J.C. Robinson, M.D. Regional Cancer Center	San Pablo	California
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St Louis	Missouri
United States	Park Nicollet Health Services	St. Louis Park	Minnesota
United States	United Hospital	St. Paul	Minnesota
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Community Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	Wilmed Radiation Oncology Services	Wilson	North Carolina
United States	Cancer Treatment Center	Wooster	Ohio
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 report — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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).	Yes
Secondary	Frequency of Patients With Persistent or Recurrent Disease Eligible for Surgical Salvage Resection		Analysis occurs with the primary outcome measure.	No