RATIONALE: Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and giving them before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase II trial to study the effectiveness of combining neoadjuvant irinotecan with cisplatin in treating patients who are undergoing surgical resection for locally advanced cancer of the stomach or gastroesophageal junction.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the stomach stage II gastric cancer stage III gastric cancer stage IV gastric cancer	Drug: cisplatin  Drug: fludeoxyglucose F 18  Drug: irinotecan  Procedure: chemotherapy  Procedure: computed tomography  Procedure: conventional surgery  Procedure: diagnostic test  Procedure: neoadjuvant therapy  Procedure: surgery  Procedure: tomography, emission computed	Phase II

Further Study Details: 

OBJECTIVES:

• Correlate the early-treatment F18-fluorodeoxyglucose positron emission tomography (FDG-PET/CT) response with histologic response and patient outcome, in terms of overall and progression-free survival, in patients with locally advanced adenocarcinoma of the stomach or gastroesophageal junction treated with neoadjuvant irinotecan and cisplatin followed by surgical resection.
• Determine the efficacy and safety of this regimen in these patients.
• Evaluate the biology of locally advanced gastric cancer and response to chemotherapy by DNA microarray and histopathology in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter study.

• Neoadjuvant chemotherapy: Patients receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1, 8, 22, and 29. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
• Surgery: Within 4 weeks after completion of neoadjuvant chemotherapy, patients undergo radical subtotal or total gastrectomy with lymph node dissection. Patients undergo fluorodeoxyglucose FDG-PET/CT at baseline. Some patients undergo additional FDG-PET/CT scans at weeks 3 and 6.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 10 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal (GE) junction
• Tumors involving the GE junction must have the bulk of disease in the stomach
• Siewert's type II and III tumors involving the GE junction are eligible
• Tumors of the distal esophagus that extend less than 2 cm into the stomach are ineligible
• Locally advanced disease that is potentially curable by surgery
• Any T, N+, M0 or T3-T4, any N, M0 by staging CT scan and laparoscopy or endoscopic ultrasound
• No T1-T2, N0, M0 tumors
• No metastatic disease
• Any suspected sites of M1 disease must be proven to be M0

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 60-100% OR
• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No history of active angina
• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past 6 months
• No history of significant ventricular arrhythmia requiring antiarrhythmic medication
• No history of clinically significant conduction system abnormality

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent serious infection
• No other uncontrolled medical illness that would preclude study participation
• No psychiatric illness that would preclude study compliance
• No clinically significant auditory impairment
• No pre-existing peripheral neuropathy grade 2 or greater
• No other active malignancy within the past 5 years except nonmelanoma skin cancer, nonmetastatic prostate cancer, or carcinoma in situ of the cervix
• Able to tolerate the proposed study surgical procedure and chemotherapy regimen

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy for this disease

Chemotherapy

• No prior chemotherapy for this disease
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this disease

Surgery

• See Disease Characteristics

Other

• No concurrent vitamins, antioxidants, or herbal preparations or supplements
• A single daily multivitamin tablet is allowed

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States; Recruiting

Study chairs or principal investigators

Manish A. Shah, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000304738; MSKCC-03032; NCI-5917; NCT00062374
Record last reviewed:  October 2004
Last Updated:  December 9, 2004
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00062374
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08