Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer

Randomized Phase II Study of Preoperative Combined Modality Paclitaxel / Cisplatin / RT or Irinotecan / Cisplatin / RT Followed by Postoperative Chemotherapy With the Same Agents in Operable Adenocarcinoma of the Esophagus

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Esophageal Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: irinotecan hydrochloride; Procedure: conventional surgery; Radiation: radiation therapy; Drug: paclitaxel

Detailed Description

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 A: Patients receive neoadjuvant radiotherapy once daily, 5 days a week, for 5 weeks beginning on day 1 concurrently with neoadjuvant chemotherapy comprising cisplatin IV (Intravenous) 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 B: Patients receive neoadjuvant radiotherapy as in arm A concurrently with neoadjuvant chemotherapy comprising paclitaxel IV (Intravenous) 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 A. 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.

ACCRUAL: A total of 97 patients (50 on Arm A and 47 on Arm B) were accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 be considered surgically resectable (T1-3, but not T4)
• Age>=18 years
• ECOG Performance status 0-1
• Adequate hematopoietic, hepatic, renal functions defined by the following within 4 weeks prior to randomization:
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• Prior curatively treated malignancy allowed if currently disease-free and survival prognosis is more than 5 years
• Fertile patients must use effective contraception
• Endoscopy with biopsy and dilation allowed

Exclusion Criteria:

• Tumor extends more than 2 cm into the cardia
• Pregnant or nursing
• Other concurrent illness that would preclude study therapy or surgical resection
• Concurrent filgrastim (G-CSF) during study radiotherapy
• Prior chemotherapy
• Prior radiotherapy
• Prior surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cisplatin / Irinotecan / Radiation therapy (Arm A); Days 1 - 35 : Concurrent radiation therapy (RT) and Cisplatin / Irinotecan Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Cisplatin 30 mg/m² days 1, 8, 22, 29. Irinotecan 65 mg/m² days 1, 8, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles	Drug: cisplatin; Days 1 - 35 : Cisplatin 30 mg/m² days 1, 8, 15, 22, 29 Days 63 - 77 : cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles; Other Names: CDDP; Platinol; platinum; DDP; Platinol-AQ; DACP; cis-platinum; NSC 119875; Drug: irinotecan hydrochloride; Days 1 - 35 : Irinotecan 65 mg/m² days 1, 8, 22, 29 Days 63 - 77 : irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles; Other Names: Camptosar; CPT-11; Camptothecin-11; Procedure: conventional surgery; The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.; Radiation: radiation therapy; The total dose to the prescription point was 4500 cGy given in 25 fractions. The patient was treated with one fraction per day with all fields treated per day. 180 cGy was delivered to the isocenter. If the dose to the supraclavicular fossa (SCF) was less than 4500 cGy, a localized photon or electron boost was allowed in order to increase the SCF dose to 4500 cGy, specified at 3 cm depth from the anterior skin surface.
Experimental: Paclitaxel / Cisplatin / Radiation therapy (Arm B); Days 1 - 35 : Concurrent radiation therapy (RT) and Paclitaxel/Cisplatin Chemotherapy. Radiotherapy 45 Gy administered at 1.8 Gy per day, 5 days a week for 5 weeks. Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29. Cisplatin 30 mg/m² days 1, 8, 15, 22, 29. Chemotherapy should begin within 24 hours of start of radiotherapy. Days 63 - 77 : Surgical Resection At least 28 days after surgical resection, begin adjuvant chemotherapy: paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles.	Drug: cisplatin; Days 1 - 35 : Cisplatin 30 mg/m² days 1, 8, 15, 22, 29 Days 63 - 77 : cisplatin 30 mg/m² and irinotecan 65 mg/m² days 1 and 8 of three 3-week cycles; Other Names: CDDP; Platinol; platinum; DDP; Platinol-AQ; DACP; cis-platinum; NSC 119875; Procedure: conventional surgery; The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.; Radiation: radiation therapy; The total dose to the prescription point was 4500 cGy given in 25 fractions. The patient was treated with one fraction per day with all fields treated per day. 180 cGy was delivered to the isocenter. If the dose to the supraclavicular fossa (SCF) was less than 4500 cGy, a localized photon or electron boost was allowed in order to increase the SCF dose to 4500 cGy, specified at 3 cm depth from the anterior skin surface.; Drug: paclitaxel; Days 1 - 35 : Paclitaxel 50 mg/m² (1 hr) days 1, 8, 15, 22, 29 Days 63 - 77 : paclitaxel 175 mg/m² and cisplatin 75 mg/m² day 1 of three 3-week cycles; Other Names: Taxol; NSC 125973

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response Rate	A patient would have achieved a pathologic complete response if no histopathological evidence of residual tumor is found in the resected esophageal specimen and nodal tissue.	approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Time	Survival was measured from the date of randomization onto study to death from any cause.Patients who were still alive at the end of the study were censored at the last date of known alive. Median survival time was calculated in the 81 eligible and treated patients.	Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry
Recurrence-free Survival Time	Recurrence-free survival is measured from the date of complete response to recurrence of the cancer. Patients without recurrence were censored at the last date of known recurrence-free. Median recurrence-free survival time was calculated in the eligible and treated patients.	Approximately 1 month after completing all treatments, then every 3 months up to 2 years, every 6 months from 2-5 years of study entry and annually 6-10 years from study entry

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Larry Kleinberg, MD, Sidney kimmel comprehensive cancer center at johns hopkins

Publications and helpful links

General Publications

• Kleinberg L, Powell ME, Forastiere AA, et al.: Survival outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma. [Abstract] J Clin Oncol 26 (Suppl15): A-4532, 2008.
• Kleinberg LR, Eapen S, Hamilton S, et al.: E1201: an Eastern Cooperative Oncology Group (ECOG) randomized phase II trial to measure response rate and toxicity of preoperative combined modality paclitaxel/cisplatin/RT or irinotecan/cisplatin/RT in adenocarcinoma of the esophagus. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-143, S80, 2006.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2002
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: April 9, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: stage IV gastric cancer; stage III gastric cancer; stage II esophageal cancer; stage III esophageal cancer; adenocarcinoma of the stomach; adenocarcinoma of the esophagus; stage IV esophageal cancer; stage I gastric cancer; stage II gastric cancer; stage I esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Neoplasms; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Paclitaxel; Cisplatin; Irinotecan; Camptothecin
• Other Study ID Numbers: CDR0000069309; U10CA021115 (U.S. NIH Grant/Contract); E1201 (Other Identifier: Eastern Cooperative Oncology Group (ECOG))