Induction Chemotherapy, FOLFIRINOX Followed With Concurrent Capecitabine and Radiation Therapy in Inoperable Locally Advanced Cancer of the Pancreas
- Conditions
- Cancer of Pancreas
- Interventions
- Drug: FOLFIRINOX + CRT
- Registration Number
- NCT02311439
- Lead Sponsor
- Assiut University
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description FOLFIRINOX + CRT FOLFIRINOX + CRT 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.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events as a Measure of Safety and Tolerability of FOLFIRINOX plus Concurrent Radiotherapy with Capecitabine 6 months after enrolment will be carried out, using (CTCAE) Common Terminology Criteria for Adverse Events, Version 4.0
- Secondary Outcome Measures
Name Time Method Tumor response 6 months after enrolment will be carried out, using (RECIST) Response Evaluation Criteria In Solid Tumors, Version 1.1
Trial Locations
- Locations (1)
Assiut University Hospitals
🇪🇬Asyut, Egypt