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

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

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.

Study Overview

• Status: Unknown
• Conditions: Locally Advanced or Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: Gemcitabine; Drug: S-1; Drug: Leucovorin(oral ); Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-FU; Drug: Leucovorin(IV)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Miaoli, Taiwan
    • National Institute of Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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.
3. Patients with prior radiotherapy are eligible if the irradiated area does not involve the only source of measurable / evaluable disease.
4. Patients' baseline ECOG performance status must be 1.
5. Patients' life expectancy 12 weeks or greater.
6. Patients' age 20 and 80.
7. Patients with biliary obstruction and adequate drainage procedures before enrollment are eligible.
8. Patients must agree to have indwelling venous catheter implanted.
9. Women or men and their partners of reproductive potential should agree to use an effective contraceptive method.
10. All patients must be informed of the investigational nature of this study and must sign and give written informed consent.

Exclusion Criteria:

1. 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.
2. Patients with central nervous system metastasis
3. Patients with active infection
4. Pregnant or breast-nursing women
5. Patients with active cardiopulmonary disease or history of ischemic heart disease
6. Patients who have peripheral neuropathy > Grade I of any etiology
7. 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.
8. 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
9. Patients who are under biologic treatment for their malignancy

10. Laboratory tests (hematology, chemistry) outside specified limits:

    1. WBC ≤ 3 x 10³/mm³
    2. ANC ≤ 1.5 x 10³/mm³
    3. Platelets ≤ 100.000/mm³
    4. Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l)
    5. GFR < 60 mL/min
    6. AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN
    7. Total bilirubin > 2 x ULN
    8. Albumin < 2.5 g/dL

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SLOG; 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: Gemcitabine; Intervention is administered to patients in this Arm.; Drug: S-1; Intervention is administered to patients in this Arm.; Drug: Leucovorin(oral ); Intervention is administered to patients in this Arm.; Drug: Oxaliplatin; Intervention is administered to patients in this Arm.
Experimental: mFOLFIRINOX; 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; Intervention is administered to patients in this Arm.; Drug: Irinotecan; Intervention is administered to patients in this Arm.; Drug: 5-FU; Intervention is administered to patients in this Arm.; Drug: Leucovorin(IV); Intervention is administered to patients in this Arm.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: National Taiwan University Hospital; China Medical University Hospital; Chang Gung Memorial Hospital; Taipei Veterans General Hospital, Taiwan; National Cheng-Kung University Hospital; Taipei Medical University Shuang Ho Hospital; Kaohsiung Medical University; Tri-Service General Hospital; E-DA Hospital
• Investigators: Study Chair: Chen Li-Tzong, National Insitute of Cancer Research

Publications and helpful links

General Publications

• Chiang NJ, Tsai KK, Hsiao CF, Yang SH, Hsiao HH, Shen WC, Hsu C, Lin YL, Chen JS, Shan YS, Chen LT. A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma-TCOG T1211 study. Eur J Cancer. 2020 Jan;124:123-130. doi: 10.1016/j.ejca.2019.10.023. Epub 2019 Nov 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 21, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Gemcitabine; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin
• Other Study ID Numbers: T5217

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No