Surgery With or Without Combination Chemotherapy in Treating Patients With Stomach Cancer

Gastric Cancer Clinical Trial

Official title:

Randomized Phase III Study of Preoperative Chemotherapy Followed by Surgery Versus Surgery Alone in Locally Advanced Gastric Cancer (cT3 and cT4NxM0)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00004099
• Other study ID #: EORTC-40954
• Secondary ID: EORTC-40954
• Status: Terminated
• Phase: Phase 3
• First received: December 10, 1999
• Last updated: September 20, 2012
• Start date: July 1999

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if surgery alone or surgery combined with chemotherapy is more effective in treating stomach cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients who have stage II, stage III, or stage IV stomach cancer.

Description:

OBJECTIVES:

• Compare overall survival in patients with locally advanced gastric cancer treated with surgery alone or in combination with neoadjuvant cisplatin, leucovorin calcium and fluorouracil.

• Compare these two regimens in terms of the rate of complete resection, time to progression, and morbidity in these patients.

• Evaluate toxicity of and disease response to neoadjuvant chemotherapy in these patients.

• Evaluate quality of life and performance status in these patients pre- and post-surgery and compare quality of life for both regimens.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to center, primary tumor category (cT3 or cT4), localization of tumor (upper third including cardia II or III vs middle and lower third), gender, and histological subtype (intestinal vs nonintestinal). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive cisplatin IV over 1 hour on days 1, 15, and 29. Patients also receive leucovorin calcium IV over 2 hours followed by fluorouracil IV over 24 hours on days 1, 8, 15, 22, 29, and 36. A second course is administered beginning 2 weeks later in the absence of disease progression or unacceptable toxicity.

Patients undergo resection and lymphadenectomy on days 57-63 of the second course of chemotherapy.

• Arm II: Patients undergo resection and lymphadenectomy within 14 days of randomization.

Quality of life is assessed before randomization, every 3 months for 1 year and at 2 years after randomization.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, then every 3 months thereafter until death.

PROJECTED ACCRUAL: A total of 360 patients (180 per arm) will be accrued for this study over 4 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 144
• Est. primary completion date: February 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven stage II-IV adenocarcinoma of the stomach including cardia carcinoma types II and III

• Locally resectable disease

• No distant metastases except M1 lymph nodes

• No evidence of peritoneal carcinomatosis

• Free tumor cells in lavage at laparoscopy allowed

• No uncontrolled bleeding of the primary tumor

• No gastric outlet syndrome or complete tumor stenosis that would require total parenteral nutrition

PATIENT CHARACTERISTICS:

Age:

• 18 to 69

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3

• Absolute neutrophil count greater than 2,000/mm^3

• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)

• Prothrombin rate at least 70%

Renal:

• Creatinine no greater than 1.25 times ULN

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No prior atrial or ventricular arrhythmias

• No prior congestive heart failure

• No myocardial infarction within the past 6 months

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other prior or concurrent neoplasm except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix

• No active infection

• No allergy to protocol drugs

• No dementia or significantly altered mental status

• No other serious medical condition that would prevent compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No filgrastim (G-CSF) within 48 hours prior to chemotherapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

• No prior stent implantation

• No prior laser therapy

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• cisplatin

• fluorouracil

• leucovorin calcium

Procedure:
• neoadjuvant therapy

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Egypt	National Cancer Institute of Egypt	Cairo
Germany	Robert Roessle Klinik	Berlin
Germany	Medizinische Klinik I	Dresden
Germany	Universitaetsklinik Duesseldorf	Duesseldorf
Germany	Department of Medicine III	Erlangen
Germany	Evangelisches Bethesda Krankenhaus GmbH	Essen
Germany	Kliniken Essen - Mitte	Essen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Krankenhaus Nordwest	Frankfurt
Germany	Universitatsklinik - Saarland	Homburg
Germany	Klinik & Poliklinik fur Strahlentherapie der Universitat zu Koln	Koln
Germany	Kreiskrankenhaus Meissen	Meissen
Germany	Westfaelische Wilhelms-Universitaet	Muenster
Germany	Klinikum Rechts Der Isar/Technische Universitaet Muenchen	Munich
Germany	Staedtisches Krankenhaus	Solingen
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Portugal	Instituto Portugues de Oncologia Centro do Porto, SA	Porto

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Egypt,  Germany,  Netherlands,  Portugal, 

References & Publications (2)

Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM. Neoadjuvant chemothe — View Citation

Schuhmacher C, Schlag P, Lordick F, et al.: Neoadjuvant chemotherapy versus surgery alone for locally advanced adenocarcinoma of the stomach and cardia: randomized EORTC phase III trial #40954. [Abstract] J Clin Oncol 27 (Suppl 15): A-4510, 2009.