RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs in different combinations and combining them with interferon alfa and G-CSF may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens in treating patients with advanced stomach cancer.

Condition	Treatment or Intervention	Phase
stage III gastric cancer recurrent gastric cancer stage IV gastric cancer	Drug: docetaxel  Drug: doxorubicin  Drug: filgrastim  Drug: fluorouracil  Drug: hydroxyurea  Drug: interferon alfa	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the objective response rates for two different regimens in patients with advanced gastric cancer: the combination of fluorouracil plus hydroxyurea given as high dose 24 hour infusions plus interferon alfa-2a and filgrastim; versus the combination of doxorubicin and docetaxel.

II. Evaluate the toxicities and reversibility of toxicities of each of these combinations in patients with advanced gastric cancer.

PROTOCOL OUTLINE: This is an open label, two arm, multicenter, randomized study.

Arm I: Patients receive fluorouracil (5-FU), recombinant alfa-2a interferon, hydroxyurea (HU), and filgrastim (granulocyte colony-stimulating factor; G-CSF). 5-FU is administered by 24 hour infusion on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Recombinant alfa-2a interferon is administered subcutaneously immediately before beginning the 5-FU infusion, then three times a week for 6 weeks. HU is administered by 24 hour infusion on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). G-CSF is administered subcutaneously on days 3, 4, 5, and 6 on weeks 1-6. Weeks 7 and 8 are rest periods.

Arm II: Patients receive doxorubicin administered by slow IV push followed (30 minutes after infusion) by docetaxel as a 1 hour IV infusion. Treatment is repeated every 21 days.

All patients are assessed monthly during study and continue study treatment as long as no disease progression or unacceptable toxic effects are observed.

Patients are followed every 3 months for the first 2 years, then every 6 months for years 2-5, and then annually thereafter.

PROJECTED ACCRUAL: A minimum of 26 patients (13 in each arm) and a maximum of 80 patients (40 in each arm) will be accrued in this study in approximately 2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction beyond the scope of surgical resection
• Must have measurable disease in either one or two dimensions either radiographically or by physical examination; Measurable disease must be documented outside of a prior radiation portal
• Evaluable disease only not allowed

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunotherapy
• Chemotherapy: No prior systemic chemotherapy
• Endocrine therapy: No chronic use of steroids; No concurrent hormonal therapy (except birth control pills)
• Radiotherapy: At least 1 month since prior radiotherapy; No concurrent palliative radiotherapy (arm I patients)
• Surgery: Must have fully recovered from surgery
• Other: At least 4 weeks since other investigational agents and recovered from all toxic effects; No chronic use of aspirin, nonsteroidal antiinflammatory agents, antianginal medications, or extraordinary antihypertensive regimens

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 4,000/mm3; Absolute neutrophil count greater than 1,500/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin no greater than upper limit of normal (ULN); SGOT no greater than 1.5 times ULN; Alkaline phosphatase no greater than 5 times ULN
• Renal: Creatinine less than 2.0 mg/dL
• Cardiovascular: No New York Heart Association class III or IV heart disease; No chronic or unstable angina; No uncontrolled congestive heart failure; No arrhythmia; No chronic angina; No myocardial infarction in the past 1 year; If history of atherosclerotic heart disease, prior cardiac catheterization or thallium stress test must not suggest coronary artery disease
• Neurology: No symptomatic peripheral neuropathy greater than grade 2; No cerebellar disease; No seizure disorder; No organic mental syndrome; No major psychoaffective disorder
• Pulmonary: No chronic obstructive pulmonary disease; No chronic bronchitis, emphysema, sarcoid, or bronchiectasis
• Other: No poorly controlled diabetes mellitus; No psychiatric illness; No active infections, including AIDS, ARC, or HIV positive; No history of hypersensitivity to products containing Polysorbate 80; No history of uncontrolled alcohol or drug abuse; No uncontrolled hypercalcemia; No other prior malignancy within the past 5 years other than nonmelanomatous skin cancer or cervical carcinoma in situ; Not pregnant or nursing; Adequate contraception required of all fertile patients

Colorado
      CCOP - Colorado Cancer Research Program, Inc., Denver,  Colorado,  80209-5031,  United States
Illinois
      CCOP - Central Illinois, Springfield,  Illinois,  62526,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      Veterans Affairs Medical Center - Chicago (Lakeside), Chicago,  Illinois,  60611,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
Massachusetts
      New England Medical Center Hospital, Boston,  Massachusetts,  02111,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018-1095,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
      University of Rochester Cancer Center, Rochester,  New York,  14642,  United States
Ohio
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Oklahoma
      CCOP - St. Francis Hospital/Natalie Warren Bryant Cancer Center, Tulsa,  Oklahoma,  74136,  United States
Pennsylvania
      Allegheny University Hospitals- Hahnemann, Philadelphia,  Pennsylvania,  19102-1192,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      University of Pennsylvania Cancer Center, Philadelphia,  Pennsylvania,  19104,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Scott Wadler,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000065978; E-6296
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003172
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08