RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well lapatinib works in treating patients with locally advanced or metastatic stomach cancer.

Condition	Treatment or Intervention	Phase
recurrent gastric cancer stage III gastric cancer stage IV gastric cancer diffuse adenocarcinoma of the stomach intestinal adenocarcinoma of the stomach mixed adenocarcinoma of the stomach	Drug: lapatinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the confirmed response (complete and partial) in patients with locally advanced or metastatic gastric cancer treated with lapatinib.
• Determine the time to treatment failure and overall survival of patients treated with this drug.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Correlate, preliminarily, protein expression and gene expression of epidermal growth factor receptor, HER2, and markers of angiogenesis with clinical outcome in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 6.7-20 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed* gastric cancer, meeting one of the following criteria:
• Locally advanced disease
• Metastatic disease
• Histological confirmation of gastric cancer from a metastatic site allowed provided gastric involvement is clinically confirmed and there is no evidence of another primary cancer NOTE: *Biopsy of the primary tumor is not required
• Any of the following histological subtypes are eligible:
• Adenocarcinoma
• Papillary carcinoma
• Mucinous carcinoma
• Intestinal type
• Clear cell adenocarcinoma
• Signet ring cell carcinoma
• Undifferentiated carcinoma
• Adenocarcinoma not otherwise specified (NOS)
• Carcinoma NOS
• Primary or recurrent disease
• Surgically incurable disease
• Measurable disease
• Site of measurable disease must be outside prior radiotherapy field
• Must be willing to submit specimens AND paraffin-embedded specimens must be available
• No carcinoid tumor or sarcoma

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of liver metastases)
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• Cardiac ejection fraction normal by echocardiogram or MUGA

Gastrointestinal

• Able to swallow and/or receive enteral medications via a gastrostomy feeding tube
• No intractable nausea or vomiting
• No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
• No malabsorption syndrome
• No requirement for IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in remission
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior neoadjuvant or adjuvant immunotherapy allowed provided therapy was completed ≥ 6 months before documentation of recurrent or metastatic disease
• No concurrent immunotherapy for gastric cancer

Chemotherapy

• Prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy allowed provided therapy was completed ≥ 6 months before documentation of recurrent or metastatic disease
• No concurrent chemotherapy for gastric cancer

Endocrine therapy

• At least 14 days since prior and no concurrent dexamethasone or dexamethasone equivalent (dose > 1.5 mg/day)
• Prior neoadjuvant or adjuvant hormonal therapy allowed provided therapy was completed ≥ 6 months before documentation of recurrent or metastatic disease
• No concurrent hormonal therapy for gastric cancer

Radiotherapy

• See Disease Characteristics
• See Chemotherapy
• Prior neoadjuvant or adjuvant radiotherapy allowed provided therapy was completed ≥ 6 months before documentation of recurrent or metastatic disease
• No concurrent radiotherapy for gastric cancer

Surgery

• At least 2 weeks since prior surgery for gastric cancer and recovered
• No prior surgical procedures affecting absorption

Other

• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
• Clarithromycin
• Erythromycin
• Troleandomycin
• Delaviridine
• Ritonavir
• Indinavir
• Saquinavir
• Nelfinavir
• Amprenavir
• Lopinavir
• Itraconazole
• Ketoconazole
• Voriconazole
• Fluconazole (doses ≤ 150 mg/day allowed)
• Nefazodone
• Fluvoxamine
• Verapamil
• Diltiazem
• Cimetidine
• Aprepitant
• Grapefruit or grapefruit juice
• Bitter orange
• At least 6 months since prior and no concurrent amiodarone
• At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:
• Phenytoin
• Carbamazepine
• Phenobarbital
• Efavirenz
• Nevirapine
• Rifampin
• Rifabutin
• Rifapentine
• Hypericum perforatum (St. John's wort)
• Modafinil
• No prior treatment for metastatic disease
• No prior epidermal growth factor receptor-targeting therapy
• No other concurrent therapy for gastric cancer
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent gastric pH modifiers, including any of the following:
• Ranitidine
• Nizatidine
• Famotidine
• Omeprazole
• Esomeprazole
• Rabeprazole
• Pantoprazole
• Lansoprazole
• Concurrent antacids allowed provided antacids are not administered within 1 hour before or after study drug administration

California
      Glendale Memorial Hospital and Health Center, Glendale,  California,  91204,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Kansas
      Associates in Womens Health, Wichita,  Kansas,  67203,  United States; Recruiting
      Cancer Center of Kansas - Chanute, Chanute,  Kansas,  66720,  United States; Recruiting
      Cancer Center of Kansas - Dodge City, Dodge City,  Kansas,  67801,  United States; Recruiting
      Cancer Center of Kansas - Kingman, Kingman,  Kansas,  67068,  United States; Recruiting
      Cancer Center of Kansas - Newton, Newton,  Kansas,  67114,  United States; Recruiting
      Cancer Center of Kansas - Salina, Salina,  Kansas,  67401,  United States; Recruiting
      Cancer Center of Kansas - Wellington, Wellington,  Kansas,  67152,  United States; Recruiting
      Cancer Center of Kansas - Winfield, Winfield,  Kansas,  67156,  United States; Recruiting
      Cancer Center of Kansas, P.A. - El Dorado, El Dorado,  Kansas,  67042,  United States; Recruiting
      Cancer Center of Kansas, P.A. - Parsons, Parsons,  Kansas,  67357,  United States; Recruiting
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Pratt Cancer Center of Kansas, Pratt,  Kansas,  67124,  United States; Recruiting
      Southwest Medical Center, Liberal,  Kansas,  67901,  United States; Recruiting
      Via Christi Cancer Center at Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
Montana
      Bozeman Deaconess Hospital, Bozeman,  Montana,  59715,  United States; Recruiting
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
      Community Medical Center, Missoula,  Montana,  59801,  United States; Recruiting
      Deaconess Billings Clinic Cancer Center, Billings,  Montana,  59107-5100,  United States; Recruiting
      Eastern Montana Cancer Center, Miles City,  Montana,  59301,  United States; Recruiting
      Kalispell Regional Medical Center, Kalispell,  Montana,  59901,  United States; Recruiting
      Montana Cancer Center at St. Patrick Hospital and Health Sciences Center, Missoula,  Montana,  59807,  United States; Recruiting
      Northern Rockies Radiation Oncology Center, Billings,  Montana,  59103,  United States; Recruiting
      St. James Community Hospital, Butte,  Montana,  59701,  United States; Recruiting
      St. Peter's Hospital, Helena,  Montana,  59601-4999,  United States; Recruiting
      St. Vincent Healthcare, Billings,  Montana,  59101,  United States; Recruiting
Wyoming
      Cancer Center of Northern Wyoming, Sheridan,  Wyoming,  82801,  United States; Recruiting

Study chairs or principal investigators

Syma Iqbal, MD,  University of Southern California   
Heinz-Josef Lenz, MD,  University of Southern California   

Study ID Numbers:  CDR0000409575; SWOG-S0413; NCT00103324
Record last reviewed:  January 2005
Last Updated:  April 4, 2005
Record first received:  February 7, 2005
ClinicalTrials.gov Identifier:  NCT00103324
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08