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

Assiut University

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Cancer of Pancreas

Treatments: Drug: FOLFIRINOX + CRT

Study type: Interventional

Funder types: Other

Identifiers

NCT02311439

LAP001

Details and patient eligibility

About

This prospective cohort, phase II, trial is studying induction chemotherapy combination, FOLFIRINOX regimen, consisted of oxaliplatin, irinotecan, leucovorin and fluorouracil (5-FU), for 4 cycles, followed by consolidation concurrent radiotherapy with capecitabine in non-progressed cases, in treating patients with locally advanced cancer pancreas.

Full description

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.

3. 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

4. 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.

Enrollment: 1 estimated patient

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Exclusion criteria

• ECOG performance status > 2
• Life expectancy < 3 months.
• Glomerular filtration rate < 30 mL/min.
• Absolute neutrophil count < 1,500/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.
• medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease)
• pregnant or nursing.
• prior chemotherapy or radiotherapy.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1 participants in 1 patient group

FOLFIRINOX + CRT

Experimental group

Description:

FOLFIRINOX regimen, consisted of oxaliplatin, irinotecan, leucovorin and fluorouracil (5-FU), for 4 cycles, followed by consolidation radiotherapy concurrent with capecitabine 625mg/m2 BID in non-progressed cases, in treating patients with locally advanced cancer pancreas.

Treatment:

Drug: FOLFIRINOX + CRT