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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00033657
First received: April 9, 2002
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Esophageal Cancer
Gastric Cancer
Drug: cisplatin
Drug: irinotecan hydrochloride
Drug: paclitaxel
Procedure: conventional surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Pathologic Complete Response Rate [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival Time [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Recurrence-free Survival Time [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 97
Study Start Date: May 2002
Study Completion Date: October 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • 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:
  • Camptothecin-11
  • CPT-11
  • Camptosar
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:
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • NSC 119875
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
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00033657

  Show 23 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Larry Kleinberg, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
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.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00033657     History of Changes
Other Study ID Numbers: CDR0000069309, U10CA021115, E1201
Study First Received: April 9, 2002
Results First Received: June 21, 2011
Last Updated: November 30, 2012
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
stage I gastric cancer
stage II gastric cancer
stage III gastric cancer
stage IV gastric cancer
stage I esophageal cancer
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
adenocarcinoma of the stomach
adenocarcinoma of the esophagus

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Camptothecin
Irinotecan
Paclitaxel
Cisplatin
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators

ClinicalTrials.gov processed this record on April 17, 2014