RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy before and after surgery may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining radiation therapy with two different chemotherapy regimens before and after surgery in treating patients who have esophageal cancer.

Condition	Treatment or Intervention	Phase
Esophageal Cancer Gastric Cancer	Drug: cisplatin  Drug: irinotecan  Drug: paclitaxel  Procedure: adjuvant therapy  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: radiosensitization  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the pathologic complete response rate in patients with adenocarcinoma of the esophagus or gastroesophageal junction treated with radiotherapy with pre- and post-operative cisplatin plus paclitaxel versus cisplatin plus irinotecan.
• Compare the survival outcome in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the tolerability of these adjuvant chemotherapy regimens after neoadjuvant chemoradiotherapy in these patients.
• Compare time to progression or recurrence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1) and stage of disease (T2-3, N0, M0 vs T1-3, N0-1, M0 or M1A). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive neoadjuvant radiotherapy once daily, 5 days a week, for 5 weeks beginning on day 1 concurrently with neoadjuvant chemotherapy comprising cisplatin IV over 2-3 hours followed by irinotecan IV over 30-60 minutes once daily on days 1, 8, 22, and 29. Four to six weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection. A minimum of 4 weeks after resection, patients receive adjuvant chemotherapy comprising cisplatin and irinotecan as above on days 1 and 8. Treatment with adjuvant chemotherapy repeats every 3 weeks for 3 courses.
• Arm II: Patients receive neoadjuvant radiotherapy as in arm I concurrently with neoadjuvant chemotherapy comprising paclitaxel IV over 1 hour followed by cisplatin IV over 2-3 hours once daily on days 1, 8, 15, 22, and 29. Patients then undergo surgical resection as in arm I. A minimum of 4 weeks after resection, patients receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours followed by cisplatin as above on day 1. Treatment with adjuvant chemotherapy repeats every 3 weeks for 3 courses. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 46-94 patients (23-47 per treatment arm) will be accrued for this study within 1.5-3 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed adenocarcinoma of the esophagus (20 cm below incisors) or gastroesophageal junction
• Stage T2-3, N0, M0 OR
• Stage T1-3, N0-1, M0 or M1A (celiac nodal metastasis)
• Tumor must not extend more than 2 cm into the cardia
• Tumor must be considered surgically resectable (T1-3, but not T4)

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine clearance at least 60 mL/min

Other:

• No other concurrent illness that would preclude study therapy or surgical resection
• Prior curatively treated malignancy allowed if currently disease-free and survival prognosis is more than 5 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent filgrastim (G-CSF) during study radiotherapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics
• No prior surgery

Other:

• Endoscopy with biopsy and dilation allowed

Colorado
      CCOP - Colorado Cancer Research Program, Incorporated, Denver,  Colorado,  80224,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
Florida
      Shands Cancer Center at the University of Florida Health Science Center, Gainesville,  Florida,  32610-100277,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611-4494,  United States
Iowa
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      St. Joseph's Hospital, Saint Paul,  Minnesota,  55102,  United States
New Jersey
      Cancer Institute of New Jersey at Robert Wood Johnson University Hospital, New Brunswick,  New Jersey,  08903,  United States
Ohio
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
      MetroHealth's Cancer Care Center at MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States
Pennsylvania
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Lankenau Cancer Center at Lankenau Hospital, Wynnewood,  Pennsylvania,  19096,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States

Study chairs or principal investigators

Larry Kleinberg, MD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000069309; ECOG-1201
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033657
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08