Salt Lake City,
The study is a prospective phase I trial of radiation therapy concurrent with capecitabine
and oxaliplatin chemotherapy in the treatment of locally advanced pancreas adenocarcinoma.
Eligibility criteria include pathologically confirmed, non-metastatic adenocarcinoma of the
pancreas that is surgically unresectable. Patients will undergo radiation therapy (28
treatments of 1.8 Gy for a total of 50.4 Gy) concurrent with capecitabine and oxaliplatin
chemotherapy. The primary objective of the study is to determine the maximum tolerated doses
of capecitabine and oxaliplatin when delivered concurrently with 50.4 Gy radiation therapy
with or without surgery in this patient population.
Secondary objectives of the study are to determine the tumor response rate, survival rate,
local control rate and the rate of distant metastases following capecitabine, oxaliplatin,
and radiation therapy with or without surgery and to determine the rate at which patients
with unresectable disease become resectable.
Patients will undergo radiation therapy (28 treatments of 1.8 Gy for a total of 50.4 Gy)
concurrent with capecitabine and oxaliplatin chemotherapy. The primary objective of the
study is to determine the maximum tolerated doses of capecitabine and oxaliplatin when
delivered concurrently with 50.4 Gy radiation therapy with or without surgery in this
Three dose levels are planned, as shown in the "Dose Escalation" table below. Three patients
are planned at each level. When 3 patients have completed an entire chemoradiation course
and are monitored for at least 2 weeks after the end of treatment without the occurrence of
dose limiting toxicities (DLTs), then the next 3 patients will be treated at the next
highest dose level. If one of the first three patients treated at any given dose level
experiences a DLT, three further patients will be treated at that level. If only one in six
patients at a given level experiences a DLT, escalation can proceed. If two or more of three
to six patients at the lowest administered dose level experience DLTs, then the MTD is below
the lowest administered dose, but no specific MTD will be defined. If two or more of three
to six patients at a higher dose level experiences DLTs, the dose preceding the lowest dose
level satisfying this criterion will be declared the MTD. If all the dose levels are
exhausted without two or more of three to six patients experiencing DLTs, then the MTD is
higher than the maximum administered dose, but no specific MTD will be defined. If MTD is
reached at a given dose level, then additional patients can be accrued to the next lowest
dose level, such that up to six patients can be accrued to the dose level below MTD. Because
three dose levels are planned, with 3 to 6 patients enrolled in each dose level, a minimum
of 9 and a maximum of 18 patients are required for trial completion.
Patient Selection Criteria
- Pathologically confirmed adenocarcinoma of the pancreas.
- No distant metastases (no metastases beyond regional lymph nodes).
- Deemed surgically unresectable by a surgical oncologist due to hepatic artery, celiac
axis, superior mesenteric artery, superior mesenteric vein, portal vein, aorta,
inferior vena cava, and/or rib/vertebral body involvement as defined by CT/MRI scan
and/or endoscopic ultrasound (EUS).
- No malignancy (within the past two years) except for non-melanomatous skin cancer or
carcinoma in situ of the cervix, uterus, or bladder.
- No previous chemotherapy for pancreatic cancer.
- No prior irradiation to the planned field.
- Zubrod performance status 0-1.
- Granulocytes > 1,800, platelets > 100,000/ul, bilirubin < 2.0 mg/dL, ALT < 3x upper
limits of normal, creatinine < 3.0 mg/dL.
- No significant infection or other coexistent medical condition.
- No pregnant or lactating women.
- Age > 18 years old.
- Signed study-specific consent form prior to registration.