• Confirmed response probability (complete and partial responses) [ Designated as safety issue: No ]
  

• Time to treatment failure [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  

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.

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