Clinical trial NCT00089024
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas stage II pancreatic cancer stage III pancreatic cancer
Sponsor: University of Nebraska
Start date: 2004-02-25; Completion date: 2014-12-01
Enrollment: 29 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients who may undergo surgery for locally advanced pancreatic cancer.

Detailed description:
OBJECTIVES:

* Determine the antitumor and clinical benefit response to neoadjuvant chemoradiotherapy comprising gemcitabine, fluorouracil, leucovorin calcium, and oxaliplatin in patients with potentially resectable locally advanced adenocarcinoma of the pancreas.
* Determine the toxic effects of this regimen in these patients.
* Determine the achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients and correlate these plasma levels with clinical toxicity associated with this regimen.
* Determine the potential importance of polymorphic variations in genomic DNA of pertinent genes (whose protein products are targets of the antineoplastic drugs used in this study) on response to and toxicity of this regimen in these patients.
* Determine the gene expression profiles of primary and metastatic pancreatic tumors before and after treatment with this regimen.

OUTLINE:

* Neoadjuvant chemotherapy: Patients receive gemcitabine IV over 30 minutes and fluorouracil IV continuously over 24 hours on days 2 and 9, and leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
* Neoadjuvant chemoradiotherapy: Beginning on day 42, patients undergo chemoradiotherapy comprising oxaliplatin IV over 2 hours on days 42, 49, 56, 63, 70, and 77 and fluorouracil IV continuously on days 42-78 with external beam radiotherapy.
* Surgery: Patients undergo surgical resection 42-56 days after completion of chemoradiotherapy.
* Adjuvant chemotherapy: After post-operative recovery, patients receive 2 additional courses of gemcitabine, fluorouracil, and leucovorin calcium. If surgical resection is not possible, patients with stable or responsive disease resume gemcitabine, fluorouracil, and leucovorin calcium indefinitely in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Arms: arm 1: see interventions
Interventions: intervention 1: fluorouracil intervention 2: gemcitabine hydrochloride intervention 3: leucovorin calcium intervention 4: oxaliplatin intervention 5: adjuvant therapy intervention 6: conventional surgery intervention 7: neoadjuvant therapy intervention 8: radiation therapy
Intervention descriptions: intervention 1: 2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 \& 2; Repeat one 3-week cycle starting day 22 intervention 2: 750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 \& 2; Repeat one 3-week cycle starting day 22 intervention 3: 20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22 intervention 4: 48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5 intervention 5: Patients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers.

If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy. intervention 6: Restaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 \[negative margins\] or R1 \[positive microscopic margins\]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated. intervention 7: Eligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU. intervention 8: A re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42).

Protocol documents: