SLOG vs mFOLFIRINOX as the First-line Treatment in Locally Advanced Uncresectable or Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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A Phase II Randomized Study.Primary objective:to investigate the 6-month progression-free survival (PFS) rate i patients receiving SLOG or mFLFIRINOX as a first-line treatment for locally advanced and metastatic pancreatic cancer.

Detailed Description
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A total of 130 patients (65patients in each arm) will be calculated, based on the assumption of a 6-month PFS rate of 45% with mFOLFIRINOX vs 60% wuth SLOG, to achieve 75% power, with a drop-out rate of 10%. Two-sided test was performed with type I error=0.10.

Official Title
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A Phase II Randomized Study of SLOG vs mFOLFIRINOX as the First-line Treatment in Locally Advanced Uncresectable or Metastatic Pancreatic Cancer

Conditions
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Locally Advanced or Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: S-1
* Drug: Leucovorin(oral )
* Drug: Gemcitabine
* Drug: Oxaliplatin
* Drug: Irinotecan
* Drug: 5-FU
* Drug: Leucovorin(IV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have cyto-/histologically confirmed, locally advanced unresectable or metastatic adenocarcinoma of the pancreas (mPAC). Patients who have disease measurable or evaluable on x-ray, CT scan, or physical examination are eligible. Patients must have no history of prior chemotherapy for PAC, except those delivered as adjuvant setting that completed at least 6 months before documentation of recurrence by imaging study. Patients with prior radiotherapy are eligible if the irradiated area does not involve the only source of measurable / evaluable disease. Patients' baseline ECOG performance status must be 1. Patients' life expectancy 12 weeks or greater. Patients' age 20 and 80. Patients with biliary obstruction and adequate drainage procedures before enrollment are eligible. Patients must agree to have indwelling venous catheter implanted. Women or men and their partners of reproductive potential should agree to use an effective contraceptive method. All patients must be informed of the investigational nature of this study and must sign and give written informed consent. Exclusion Criteria: Patients who have major abdominal surgery, radiotherapy or other investigating agents within 4 weeks are not eligible. Patients who have palliative radiotherapy for bony metastasis will be eligible 2 weeks after the completion of radiotherapy. Patients with central nervous system metastasis Patients with active infection Pregnant or breast-nursing women Patients with active cardiopulmonary disease or history of ischemic heart disease Patients who have peripheral neuropathy > Grade I of any etiology Patients who have serious concomitant systemic disorders incompatible with the study, i.e. poorly controlled diabetes mellitus, auto-immune disorders, cirrhosis of the liver, and the rest will be at the discretion of in-charged investigator. Patients who have other prior or concurrent malignancy except for adequately treated in situ carcinoma of cervix or adequately treated basal cell carcinoma of skin, or any malignancy remains disease-free for 3 or more years after initial curative treatment Patients who are under biologic treatment for their malignancy Laboratory tests (hematology, chemistry) outside specified limits: WBC ≤ 3 x 10³/mm³ ANC ≤ 1.5 x 10³/mm³ Platelets ≤ 100.000/mm³ Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) GFR < 60 mL/min AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN Total bilirubin > 2 x ULN Albumin < 2.5 g/dL

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLOG<br>800 mg/m2 gemcitabine at a fixed rate of 10 mg/m2/min followed by a 2-hour intravenous infusion of oxaliplatin on day 1 plus twice daily oral S-1 80-120 mg/day (based on BSA) and oral leucovorin 30 mg twice a day on day 1 to day 7, every 14 days as a cycle | Drug: S-1<br>* Intervention is administered to patients in this Arm.<br>Drug: Leucovorin(oral )<br>* Intervention is administered to patients in this Arm.<br>Drug: Gemcitabine<br>* Intervention is administered to patients in this Arm.<br>Drug: Oxaliplatin<br>* Intervention is administered to patients in this Arm.<br>|
| Experimental: mFOLFIRINOX<br>oxaliplatin at a dose of 85 mg/m2, given as a 2-hour infusion, with the addition, after 30 minutes, of irinotecan at a dose of 150 mg/m2, given as a 90-minute infusion. The treatment was immediately followed by a continuous intravenous infusion via central venous catheter of leucovorin 400 mg/m2 given as a 2-hour infusion and 5-FU 2400 mg/m2 over a 46-hour period on day 1 every 14 days/cycle. | Drug: Oxaliplatin<br>* Intervention is administered to patients in this Arm.<br>Drug: Irinotecan<br>* Intervention is administered to patients in this Arm.<br>Drug: 5-FU<br>* Intervention is administered to patients in this Arm.<br>Drug: Leucovorin(IV)<br>* Intervention is administered to patients in this Arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival (PFS) | The 6-month PFS rates of the two arms are assumed to be 60% (SLOG) vs. 45% (mFOLFIRINOX) | Since this is an exploratory trial, it takes a sample size of 61 patients per arm entered in 2 years with a minimum 1 year of follow up to reach 75% power with type I error of 10% under the assumptions of exponential survival functions. |