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

NCT ID: NCT00069953

Last Updated: 2017-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2016-12-31

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.

Conditions

Esophageal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

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

cisplatin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

During induction therapy, patients receive 200 mg/m\^2/day by IV over 2 hours on days 1 and 29.

conventional surgery

Intervention Type: PROCEDURE

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

radiation therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: BIOLOGICAL

pegfilgrastim

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

Intervention Type: BIOLOGICAL

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.

Intervention Type: 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.

Intervention Type: DRUG

paclitaxel

During induction therapy, patients receive 200 mg/m\^2/day by IV over 2 hours on days 1 and 29.

Intervention Type: DRUG

conventional surgery

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

Intervention Type: PROCEDURE

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.

Intervention Type: RADIATION

Other Intervention Names

G-CSF; PEG-G-CSF; 5-FU

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NRG Oncology

OTHER

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen G. Swisher, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Providence Saint Joseph Medical Center - Burbank

Burbank, California, United States

Saint Rose Hospital

Hayward, California, United States

Providence Holy Cross Cancer Center

Mission Hills, California, United States

CCOP - Bay Area Tumor Institute

Oakland, California, United States

Summit Medical Center

Oakland, California, United States

Valley Care Medical Center

Pleasanton, California, United States

J.C. Robinson, M.D. Regional Cancer Center

San Pablo, California, United States

University of Colorado Cancer Center at University of Colorado Health Sciences Center

Aurora, Colorado, United States

Hospital of Saint Raphael

New Haven, Connecticut, United States

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States

Gulf Coast Cancer Treatment Center

Panama City, Florida, United States

Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Mount Sinai Hospital Medical Center

Chicago, Illinois, United States

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Wendt Regional Cancer Center at Finley Hospital

Dubuque, Iowa, United States

Ochsner Clinic of Baton Rouge

Baton Rouge, Louisiana, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Green Bay Oncology, Limited - Escanaba

Escanaba, Michigan, United States

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Green Bay Oncology, Limited - Iron Mountain

Iron Mountain, Michigan, United States

Foote Hospital

Jackson, Michigan, United States

Sparrow Regional Cancer Center

Lansing, Michigan, United States

Seton Cancer Institute - Saginaw

Saginaw, Michigan, United States

St. John Macomb Hospital

Warren, Michigan, United States

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States

Fairview Southdale Hospital

Edina, Minnesota, United States

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States

Virginia Piper Cancer Institute at Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Hubert H. Humphrey Cancer Center at North Memorial Medical Center

Robbinsdale, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Park Nicollet Health Services

Saint Louis Park, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

Ridgeview Medical Center

Waconia, Minnesota, United States

Hattiesburg Clinic, P.A.

Hattiesburg, Mississippi, United States

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, United States

St. John's Regional Health Center

Springfield, Missouri, United States

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, United States

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Monmouth Medical Center

Long Branch, New Jersey, United States

Fox Chase Virtua Health Cancer Program - Marlton

Marlton, New Jersey, United States

Booker Cancer Center at Riverview Medical Center

Red Bank, New Jersey, United States

Community Regional Cancer Center at Community Medical Center

Toms River, New Jersey, 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

SUNY Downstate Medical Center

Brooklyn, New York, United States

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States

Wayne Radiation Oncology

Goldsboro, North Carolina, United States

Rutherford Hospital

Rutherfordton, North Carolina, United States

Wilmed Radiation Oncology Services

Wilson, North Carolina, United States

Akron City Hospital

Akron, Ohio, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital

Dayton, Ohio, United States

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Cancer Care Center

Dayton, Ohio, United States

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States

CCOP - Dayton

Dayton, Ohio, United States

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

Middletown Regional Hospital

Middletown, Ohio, United States

Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford

Salem, Ohio, United States

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Cancer Treatment Center

Wooster, Ohio, United States

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Delaware County Regional Cancer Center at Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, United States

Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States

Rose Ramer Cancer Clinic at Anderson Area Medical Center

Anderson, South Carolina, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Cottonwood Hospital Medical Center

Murray, Utah, United States

McKay-Dee Hospital Center

Ogden, Utah, United States

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, United States

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

Schiffler Cancer Center at Wheeling Hospital

Wheeling, West Virginia, United States

Green Bay Oncology, Limited at St. Vincent Hospital

Green Bay, Wisconsin, United States

Green Bay Oncology, Limited at St. Mary's 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

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, United States

Green Bay Oncology, Limited - Oconto Falls

Oconto Falls, Wisconsin, United States

Green Bay Oncology, Limited - Sturgeon Bay

Sturgeon Bay, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21507583 (View on PubMed)

Other Identifiers

CDR0000306455

Identifier Type: -

Identifier Source: secondary_id

RTOG-0246

Identifier Type: -

Identifier Source: org_study_id