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

NCT ID: NCT00033657

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-15
• Study Completion Date: 2009-10-31

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.

Conditions

Esophageal Cancer; Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

conventional surgery

Intervention Type: PROCEDURE

The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.

radiation therapy

Intervention Type: RADIATION

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.

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.

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

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

paclitaxel

Intervention Type: DRUG

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

conventional surgery

Intervention Type: PROCEDURE

The type of resection (lvor-Lewis, Transhiatal, etc.) was left to the discretion of the operating surgeon. One lymph node dissection was required.

radiation therapy

Intervention Type: RADIATION

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.

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

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.

Intervention Type: RADIATION

Other Intervention Names

cis-platinum; platinum; Platinol; Platinol-AQ; DDP; CDDP; DACP; NSC 119875; Camptothecin-11; CPT-11; Camptosar; Taxol; NSC 125973

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Larry Kleinberg, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

CCOP - Colorado Cancer Research Program, Incorporated

Denver, Colorado, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Shands Cancer Center at the University of Florida Health Science Center

Gainesville, Florida, United States

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, 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

Cancer Institute of New Jersey at Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Ireland Cancer Center

Cleveland, Ohio, United States

MetroHealth's Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - Scott and White Hospital

Temple, Texas, 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

Countries

United States

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

Other Identifiers

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

E1201

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000069309

Identifier Type: -

Identifier Source: org_study_id