Induction Chemotherapy, FOLFIRINOX Followed With Concurrent Capecitabine and Radiation Therapy in Inoperable Locally Advanced Cancer of the Pancreas

Design \& Methodology:

1. Nature of the study: It is ( prospective cohort study).
2. Study subjects: *Target Population: Patients, fulfilling the inclusion criteria for the research, will be selected from Assiut clinical oncology department in Assiut University Hospitals.

• Sample size: 20 patients.
• Characteristics of subjects:
• Inclusion criteria: Disease characteristics:
• Histological and radiological confirmation of locally advanced cancer pancreas
• Inoperable disease
• Disease must be able to be encompassed within a radical radiotherapy treatment volume
• Not metastatic Patient characteristics:
• ECOG performance status 0 or 1
• Life expectancy > 3 months.
• Glomerular filtration rate ≥ 60 mL/min.
• WBC > 3,000/mm³.
• Absolute neutrophil count > 1,500/mm³.
• Hemoglobin > 10.0 g/dL.
• Platelet count > 100,000/mm³.
• Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN)
• Gamma-glutamyl-transferase < 1.5 times ULN.
• Transaminases ≤ 1.5 times ULN.
• Bilirubin ≤ 1.5 times ULN.
• No medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease)
• Not pregnant or nursing.
• No other previous or current malignant disease likely to interfere with protocol treatment or comparisons
• No prior chemotherapy or radiotherapy.

1. Patients \& Methods: Patients are randomized to one treatment arm. Induction 4 times chemotherapy, FOLFIRINOX regimen, consisted of Oxaliplatin at a dose of 85 mg/m2 on day 1 only, administered as a 2-hour intravenous infusion, with the addition, after 30 minutes, of Irinotecan at a dose of 180 mg/m2 on day 1 only given as a 90-minute intravenous infusion. immediately will be followed by Leucovorin at a dose of 200 mg/m2, given as a 2- hour intravenous infusion, day 1 and day 2 This treatment will be followed by fluorouracil (5-FU) dosed at 400 mg/m2, administered as an intravenous bolus on day 1 and day 2, followed by a continuous intravenous infusion of 600 /m2 over a 20- hours period on day 1 and day 2. Treatment will be administered every 2 weeks. G-CSF will be administrated according to the need. In non-progressed cases, induction chemotherapy will be followed by consolidation radiotherapy concurrent with capecitabine 625 mg/m2 BID. Radiotherapy : A fractionated dose of 50.4Gy /28 fraction/15 MeV photon energy generated by Dual-energetic Linear Accelerator.

• Gross Target Volume (GTV): visible tumor and lymph nodes.
• Clinical Target Volume (CTV): [tumor/ affected lymph node + 1-2 cm] + regional lymphatics Lymphatics :corpus: upper and lower pancreaticoduodenal, superior and inferior pancreatic, celiac Head: corpus lymphatics + porta hepatis lymphatics Tail: corpus lymphatics (except pancreaticoduodenal LN) + splenic hilum LN
• PTV: CTV + 1-1.5 cm
• All patients will undergo a complete classical evaluation at the time of presentation which will be enrolled in a separate sheet for each patient. This will include a detailed history with estimation of the age of onset, the duration of the disease,.
• Detailed physical examination will be carried out Treatment evaluation . Laboratory examination include
• complete blood count (CBC),
• liver function test (LFT)
• Renal function test (RFT),
• Serum electrolytes at presentation and before each cycle of chemotherapy. Radiographic examination include
• Abdominal Multi Detector Computed Tomography (MDCT Abdomen )
• Chest X-ray Before starting treatment, 2 weeks after ending phase 1 of treatment then 4 weeks after ending phase 2 of treatment then every 3 months for 18 months. ● Bone scan will be done in those complaining from bone pain; elevated serum alkaline phosphatase or transaminase level
• Quality of life is assessed at baseline, monthly for 6 months, and then at each follow-up visit. After completion of study treatment, patients are followed periodically. Response Assessment : will be carried out, using (RECIST) Response Evaluation Criteria In Solid Tumors, Version 1.1 Chemotherapy Toxicity Assessment: will be carried out, using (CTCAE) Common Terminology Criteria for Adverse Events, Version 4.0

1. Data analysis:

Data will be analysed using the computer program, Statistical Package for the Social Science (SPSS V.16).

Expected outcomes:

The outcome of the study will be compared statistically with previous local and international trails.

Ethical considerations:

1. Risk-benefit assessment: There is an acceptable risk may affect the patient in this research study as regard the acceptable side effects of Gemcitabine, Oxaliplatin and radiotherapy.
2. Confidentiality: Any data taken from the patient either from history, the examination or the investigations will be very confidential.
3. Research statement: All patients subjected to this study will be informed about the procedures of the research.
4. Informed consent: The study procedures will be discussed to all patients and consent will be taken from them.
5. Other ethical concerns:

The research will be conducted only by scientifically qualified and trained personnel.