Clinical trial NCT00033657: Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: 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
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Pathologic Complete Response Rate
timeFrame: 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 outcomes:
measure: Overall Survival Time
timeFrame: 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
measure: Recurrence-free Survival Time
timeFrame: 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
Other outcomes:
Locations:
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Gainesville
country: United States
facility: Shands Cancer Center at the University of Florida Health Science Center
state: Florida
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: St. Joseph's Hospital
state: Minnesota
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
state: New Jersey
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth's Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Larry Kleinberg, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.