A Phase I Study, With Expanded Cohort, of Biweekly Fixed-dose Rate Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic and Biliary Carcinomas
- Histologically-confirmed pancreatic adenocarcinoma or biliary tract carcinoma
(cholangiocarcinoma or gallbladder cancer)
- Disease must not be amenable to surgical resection. Patients with either locally
advanced or metastatic disease are eligible
- No prior systemic therapy for their diagnosis
- ECOG performance score of 0-1
- Evidence of either or both of the following:
1. RECIST-defined measurable disease (lesions that can be accurately measured in at
least one dimension with the longest diameter ≥ 20mm using conventional
techniques or ≥10 mm with spiral CT scan)
2. An elevated serum CA19-9 at baseline ( ≥ 2X ULN)
- Female patients must be either surgically sterile or postmenopausal, or if of
childbearing potential must have a negative pregnancy test (serum or urine) prior to
enrollment and agree to use effective barrier contraception during the period of
therapy. Oral, implantable, or injectable contraceptives may be affected by
cytochrome P450 interactions, and are therefore not considered effective for this
study. Male patients must be surgically sterile or must agree to use effective
contraception during the period of therapy. The definition of effective contraception
will be based on the judgment of the investigator.
- Adequate bone marrow function:
1. ANC ≥ 1500/uL
2. platelet count ≥ 100,000/uL
3. hemoglobin ≥ 9.0 g/dL
- Adequate hepatic function:
1. Total bilirubin ≤ 1.5 X ULN
2. AST (SGOT) ≤ 2.5 X ULN
3. ALT (SGPT) ≤ 2.5 X ULN
- Adequate renal function as determined by either:
1. Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated
creatinine clearance, Cockroft-Gault equation will be used)
2. Serum creatinine ≤ 1.5 X ULN
- Ability to swallow oral medications
- Ability to understand the nature of this study protocol and give written informed
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.
- Any prior systemic or investigational therapy for metastatic or locally advanced
pancreatic cancer or biliary cancer. Systemic therapy administered alone or in
combination with radiation in the adjuvant setting is permissible as long as it was
completed > 6 months prior to the time of study enrollment.
- Inability to comply with study and/or follow-up procedures.
- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that, in the opinion of the investigator, renders the subject at high risk from
treatment complications or might affect the interpretation of the results of the
- Presence of central nervous system or brain metastases.
- Pregnancy (positive pregnancy test) or lactation.
- Prior malignancy except for adequately treated basal cell skin cancer, in situ
cervical cancer, adequately treated Stage I or II cancer from which the patient is
currently in complete remission, or any other form of cancer from which the patient
has been disease-free for 5 years.
- Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmias not well controlled with medication)
or myocardial infarction within the last 12 months.
- Lack of physical integrity of the upper gastrointestinal tract or malabsorption
- Known, existing uncontrolled coagulopathy.
- Major surgery within 4 weeks of the start of study treatment, without complete
- Concurrent/pre-existing use of coumadin.