Chemoradiation in Locally Advanced Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as fluorouracil and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Interferon alfa may interfere with the growth of tumor cells. Giving combination chemotherapy and radiation therapy together with interferon alfa before surgery may shrink the tumor so it can be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving combination chemotherapy and radiation therapy together with interferon alfa works in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the effect of neoadjuvant chemoradiotherapy and interferon alfa on converting patients with locally advanced unresectable adenocarcinoma of the pancreas to resectability. Secondary Determine the rate and severity of early and late toxic effects of these regimens in these patients. Improve surgical morbidity profile and overall survival of patients who undergo surgical resection. Determine overall and progression-free survival of patients treated with this regimen. OUTLINE: This is an pilot, single center study. Part 1 (neoadjuvant therapy): Patients receive fluorouracil IV continuously over 24 hours on days 1-38; cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36; and interferon alfa subcutaneously on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, and 38. Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients then undergo restaging. Patients with resectable disease undergo surgery, and 4-10 weeks later, proceed to part 2. Patients with unresectable disease proceed directly to part 2, 4 weeks after completion of neoadjuvant therapy. Part 2 (chemotherapy): Patients receive fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 56 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with unresectable disease undergo restaging after each course of fluorouracil. If the tumor subsequently becomes resectable, patients then undergo surgery. After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

Official Title
-----------------
A Phase II Pilot Study of Multi-Agent Neo-Adjuvant Chemoradiation in Patients With Locally Advanced Pancreatic Adenocarcinoma

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Biological: recombinant interferon alfa
* Drug: cisplatin
* Drug: fluorouracil
* Radiation: radiation therapy
* Procedure: Resection of tumor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must have newly diagnosed computated tomography (CT) and endoscopic ultrasound(EUS) stage Tx-4, N0-1, M0 adenocarcinoma of pancreas according to the American Joint Committee on Cancer (AJCC) staging system. The following cell types will NOT be eligible: adenosquamous carcinoma, ampullary carcinoma, carcinoid tumor, cystadenocarcinoma, cystadenoma, distal common bile duct carcinoma, duodenal carcinoma, or islet cell carcinoma Treatment must begin within 60 days of diagnosis Must have locally advanced inoperable pancreatic cancer with no metastatic spread as determined by a baseline diagnostic CT scan of the chest, endoscopic ultrasound and CT scan with intravenous (IV) contrast (or MRI) of abdomen/pelvis, within 30 days prior to registration. No prior systemic chemotherapy or radiation therapy for pancreatic cancer Documented Eastern Cooperative Oncology Group (ECOG/Zubrod) performance status 0-1 within 14 days prior to registration Adequate hematologic, renal and hepatic function as defined by the following laboratory values (completed within 14 days prior to registration) white blood cell (WBC) > 3,000 mm3 absolute neutrophil count (ANC) > 1,500 mm3 platelet count ≥ 100,000 mm3 hemoglobin > 9.5 g/dl serum creatinine < 1.5 times institutional upper limit of normal (ULN) total bilirubin ≤ 3 mg/dl AST (SGOT) < 4.0 times institutional ULN ALT (SGPT) < 4.0 times institutional ULN alkaline phosphatase < 2.0 times institutional ULN Age ≥ 18 years Life expectancy ≥ 12 weeks Patient (male or female) of reproductive potential are required to use a medically acceptable contraception during treatment and for 3 months after the last dose of chemotherapy. Not pregnant or breastfeeding since the drugs used in this study are Pregnancy Category D: Clear evidence of risk in pregnancy. A negative pregnancy test is required within 7 days of registration if pre- or perimenopausal (i.e., last menstrual period within one year of registration) If patient has a previous diagnosis of cancer, all of the following criteria must be met and documented in the patient's medical record: Patient has undergone potentially curative therapy for all prior malignancies. No evidence of prior malignancies for at least 5 years (except for successfully treated cervical carcinoma in situ, carcinoma in situ of the breast, or nonmelanoma skin cancer. No evidence of recurrence of any prior malignancy. Patient who is receiving chronic immunotherapy (e.g. prednisone or methotrexate) for collagen vascular disease or other chronic immunologic abnormality are not eligible. Not requiring one or more of the contraindicated medications Patient must be able to understand the potential risks and benefits associated with this study. Patient able to give informed consent and would likely to comply with the study parameters.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pancreatic Adenocarcinoma Patients<br>Pancreatic Adenocarcinoma Patients treated with chemotherapy regimen and radiation (and or surgery). | Biological: recombinant interferon alfa<br>* administered subcutaneously (SQ)at a dose of 3 million units Day 1,3, and 5 each week in Cycle 1<br>* Other names: IFN-alpha-2b;Drug: cisplatin<br>* administered at a dose of 30 mg/m2 intravenously (IV) day 1 each week in Cycle 1<br>* Other names: cis-diamminedichloroplatinum(II) (CDDP);Drug: fluorouracil<br>* administered at a dose of 175 mg/m^2/day continuous infusion (CI) for 38 days in Cycle 1 and then 500 mg/m^2 intravenously (IV) each week for 6 weeks followed by a 2 week rest (1 cycle = 8 weeks)in Cycle 2 and 3<br>* Other names: 5-FU;Radiation: radiation therapy<br>* 5040 cGy total, in 28 fractions, at 180 cGy/fraction daily, Monday -Friday, for 5½ weeks (days 1-5, 8-12, 15-19, 22-26, 29-33, 36-38).<br>Procedure: Resection of tumor<br>* After Cycle 1 treatment (if resectable)- In the absence of metastatic disease, special emphasis will be paid to the local tumor. Evaluation of the growth/regression of the tumor will be made as it relates to resectability. Surgical exploration will start with a diagnostic laparoscopy. If no evidence of carcinomatosis, liver metastases or other evidence of metastatic disease is encountered, then a laparotomy will be performed. In the absence of clear technical unresectability, a radical pancreaticoduodenectomy, distal or total pancreatectomy (and resection of any involved structures) will be performed as mandated by tumor anatomy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients in Whom Tumor Was Resectable | Tumor response is measured in terms of resectability, as measured by CT scan at 2 weeks after completion of each course. A CT scan of the chest abdomen and pelvis will be performed in order to evaluate for the presence of metastatic disease. If no metastatic disease, emphasis will be paid to the local tumor. Evaluation of the growth/regression of the tumor will be made as it relates to resectability. If potential for resection then surgery will be recommended. This protocol will be followed after each cycle. | Up to 5 Years or Until Disease Progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | In all patients, measured from the date of the patient's registration in this study, until the date of the patient's death or date last known alive (if observation was censored). | Up to 5 Years or Date of Death, Whichever Occurred First | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I pancreatic cancer, stage II pancreatic cancer, stage III pancreatic cancer, adenocarcinoma of the pancreas