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

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00033657
• Other study ID #: CDR0000069309
• Secondary ID: U10CA021115E1201
• Status: Completed
• Phase: Phase 2
• Start date: August 15, 2002
• Est. completion date: October 2009

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: October 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms
• Gastric Cancer
• Stomach Neoplasms

Intervention

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
• 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
• 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

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.

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	MetroHealth's Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Cancer Institute of New Jersey at Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	St. Joseph's Hospital	Saint Paul	Minnesota
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 wit

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 adenocar

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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