New Brunswick,
New Jersey
08903
Purpose:
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor
cells and either kill them or deliver tumor-killing substances to them without harming
normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor
cells.
PURPOSE: Phase II trial to study the effectiveness of gemcitabine and trastuzumab in
treating patients who have metastatic cancer of the pancreas that overexpresses HER2/neu.
Study summary:
OBJECTIVES:
- Determine the response rate and survival of patients with metastatic pancreatic cancer
and overexpression of HER2/neu treated with gemcitabine and trastuzumab.
- Determine the toxic effects of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive gemcitabine IV over 30 minutes once weekly during weeks 1-7. Patients
receive trastuzumab IV over 90 minutes once during week 1 and trastuzumab IV over 30-90
minutes once weekly during weeks 2-8.
Patients with stable or responding disease receive gemcitabine IV over 30 minutes once
weekly during weeks 1-3 and trastuzumab IV over 30 minutes once weekly during weeks 1-4.
Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year and then every 6 months thereafter.
PROJECTED ACCRUAL: A maximum of 41 patients will be accrued for this study over 18-24
months.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically proven metastatic pancreatic cancer with overexpression of HER2/neu
- Patients in whom there is inadequate tissue to evaluate for HER2/neu overexpression
but who have elevated serum HER2/neu antigen levels are eligible
- Radiographically measurable disease
- May have metastatic disease in which primary lesion is measurable but metastatic
lesions are not measurable
- Ascites is not measurable
PATIENT CHARACTERISTICS:
Age:
- Over 18
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Granulocyte count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic:
- Bilirubin no greater than 3.0 mg/dL
- Greater than 3 times normal if increase in bilirubin is due to biliary
obstruction from tumor as long as biliary system is stented or bypassed and
bilirubin, SGOT, or SGPT is stable or decreasing
- SGOT no greater than 3 times normal
- No greater than 5 times normal if liver metastases present OR
- Greater than 5 times normal if increase in SGOT or SGPT is due to biliary
obstruction from tumor as long as biliary system is stented or bypassed and
biliary SGOT or SGPT is stable or decreasing
Renal:
- Creatinine no greater than 2.0 mg/dL
Cardiovascular:
- No unstable angina
- No prior congestive heart failure
- No prior myocardial infarction
- LVEF at least 45% by MUGA or echocardiogram
Other:
- Not pregnant
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior trastuzumab
- No concurrent growth factors
Chemotherapy:
- No prior anthracyclines
- No prior gemcitabine except prior low dose (no greater than 300 mg/m2/week)
gemcitabine with radiotherapy
- At least 6 months since prior adjuvant therapy
- More than 2 weeks since other prior chemotherapy
- No other concurrent cytotoxic chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- See Chemotherapy
- More than 2 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery:
- Not specified
Other:
- No other concurrent investigational agents