UAB Clinical Trial

UAB 0133

A Phase I/II Open Label Study of Capecitabine with Concurrent Radiotherapy for Patients with Locally Advanced, Unresectable Pancreatic Cancer

Principal Investigator: Muhammad Wasif Saif, M.D.

Objectives

Phase I

To establish a recommended Phase II dose of combined administration of Capecitabine with concurrent radiotherapy for patients with locally advanced, unresectable pancreatic cancer.

To evaluate all toxicities associated with this combination chemoradiotherapy regimen.

Phase II

To obtain the objective response rate to combined chemoradiotherapy when Capecitabine is administered at a dose level determined from the Phase I part of the study.

To characterize the quantitative and qualitative toxicities of the combined Capecitabine-radiotherapy regimen in this patient population.

To measure the time to event efficacy variables including:
- Duration of response to responding patients
- Time to disease progression
- Median survival time

Patient Selection Criteria

Inclusion Criteria

Patients must have primary/newly diagnosed unresectable disease based on institutional standardized criteria of unresectability, or residual disease after resection (macroscopic residual) as long as there is measurable disease on the post-operative CT or MRI scan, or locally recurrent disease following radical surgery in patients who have not previously received radiation therapy with 5-FU-based chemotherapy. There must be no evidence of metastatic disease in the major viscera and no peritoneal seeding.

All known malignant disease must be encompassed within a single irradiation field (15 x 15 cm maximum).

All patients must have radiographically measurable or evaluable disease: CT with 5mm cuts or spiral CT. A pretreatment arteriogram (HA and SMA with delayed views of portal vein) may be necessary in selected patients to determine major vascular invasion of resectability.

Patients with biliary or gastro-duodenal obstruction must have drainage or bypass prior to starting chemoradiation.

Patients should have adequate hepatic function as indicated by a serum bilirubin < 2mg/dL and aspartate transaminase (AST, SGOT) levels < 2.5 x upper limits of normal. Patients with elevated bilirubin due to obstruction should be stented and their bilirubin should decrease to < 2mg/dL prior to study entry.

Patients should have an absolute granulocyte count > 2000/uL, a platelet count > 100,000/uL, and an adequate renal function as indicated by a serum creatinine < 1.6mg/dL or cratinine clearance > 50mL/min.

Oral intake (includes J-tube feedings) of > 1500 calories/day should be maintained.

Exclusion Criteria

No prior 5-FU based chemotherapy or radiotherapy to the planned field will be allowed.

Gemzar (gemcitabine) as a single agent is not used as a standard treatment in such patients (locally advanced pacreatic cancer). Patients who have previously received radiation with Gemzar will be excluded from the studies. However, in a rare case where Gemzar alone was used for such patients, patient will be accepted for the protocol as long as it has been completed at least 4 weeks prior to study entry.

Pregnant women and nursing mothers are ineligible due to the possible risk of adverse effects in the newborn. Eligible patients of reproductive potential should use adequate contraception.

Serious concurrent medical illness which would jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety.

Patients with active infections requiring intravenous antibiotic therapy are not eligible until the infection has resolved.

Patients who are HIV antibody positive are ineligible as this condition may jeopardize the ability of the patient to receive this cytotoxic chemotherapy-radiotherapy program with reasonable safety.

Patients with primary CNS malignancies and CNS metastatic disease are ineligible.

Patients with known hypersensitivity or a history of marked intolerance to 5-FU are ineligible.

Because cimetidine can decrease the clearance of 5-FU, patients should not enter on this study until cimetidine is discontinued.

Patients should not receive concurrent therapy with either sorivudine or brivudine while receiving Capecitabine. If a patient has received prior sorivudine or brivudine, then at least four weeks must elapse before the patient recovers Capecitabine therapy.

Clinically significant cardiac disease not well controlled with medication (i.e., congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmias) or myocardial infarction within the last 12 months.