Peri-operative SLOG for Localized Pancreatic Cancer

Peri-operative S-1/Leucovorin, Oxaliplatin and Gemcitabine (SLOG) for Localized Pancreatic Cancer

1. To evaluate the efficacy of neoadjuvant chemotherapy SLOG in localized pancreatic cancer
2. To evaluate the safety profile in patients with pancreatic cancer who receive neoadjuvant SLOG
3. To collect tumor tissue and peripheral blood samples from the patients for a comprehensive biomarker evaluation

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma; Pancreas Cancer
• Intervention / Treatment: Drug: S-1, leucovorin, oxaliplatin and gemcitabine

Detailed Description

The role of neoadjuvant treatment in pancreatic adenocarcinoma is still under debate due to a relative lack of robust data compared with other gastrointestinal cancers. According to 2020 NCCN guidelines, neoadjuvant is now the accepted approach for borderline resectable (BR) disease, while upfront surgery is still the recommendation for resectable disease except in cases with high risk features. Another important advantage of treatment with neoadjuvant treatment is an increase in the proportion of patients who receive chemotherapy. Traditionally, only patients with a good performance status and a good recovery after surgery are treated with adjuvant chemotherapy. About 45% of patients do not receive adjuvant chemotherapy after resection due to poor performance status, postoperative morbidity, or early progression of disease. A small cohort study using total neoadjuvant FOLFIRINOX for borderline resectable pancreatic cancer yielded a promising result but the tolerability of FOLFIRINOX limited the use of this regimen in Asian population. In previous T1211 clinical trial, the SLOG regimen showed comparable efficacy with a better safety profile in metastatic pancreatic cancer. This phase II trial will evaluate the feasibility of SLOG regimen in patients with localized pancreatic cancer.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan
    • Recruiting
    • Kaohsiung Medical University Hospital
    • Contact: Hui-Ching Wang, MD; Phone Number: +8867-3121101; Email: hcwang@kmu.edu.tw
    • Principal Investigator: Hui-Ching Wang
  • Tainan, Taiwan
    • Recruiting
    • National Cheng-Kung University Hospital
    • Contact: Yung-Yeh Su, MD; Phone Number: 65181 +886-6-7000123; Email: yysu@nhri.edu.tw
    • Principal Investigator: Li-Tzong Chen, MD, PhD
  • Tainan, Taiwan
    • Recruiting
    • National Institute of Cancer Research
    • Contact: Yung-Yeh Su, MD; Phone Number: 65181 +8867-7000123; Email: yysu@nhri.edu.tw
    • Principal Investigator: Li-Tzong Chen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A. Localized resectable or potentially resectable pancreatic cancer as determined by image modality; resectability is determined by the treating surgeon No prior treatment for pancreatic cancer

B. Patients must agree to receive biopsy for histological diagnosis and provide residual tissue for biomarker analysis before chemotherapy

C. Patients must agree to provide tissue for biomarker analysis after neoadjuvant chemotherapy, either surgical specimen or follow-up biopsy in unsectable disease

D. At least one measurable lesion according to RECIST version 1.1

E. Ability to understand and willingness to sign a written informed consent document.

F. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

G. Age of 20 years or above

H. Life expectancy of at least 12 weeks

I. Adequate organ function as defined by the following criteria:

• absolute neutrophil count (ANC) ≥ 1,500/mm3
• hemoglobin level ≥ 9 g/dL
• platelet count ≥ 100,000/mm3
• total bilirubin < 2 mg/dL
• aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
• creatinine clearance rate (CCr) ≥ 50 mL/min (24-hour urine collection or calculated by Cockroft-Gault formula; male: [(140 - age) × weight (kg)]/[72 × serum creatinine(mg/dL)];female=male x 0.85

J. Patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study.

Exclusion Criteria:

A. Other malignancy within the past 5 years except for adequately treated localized skin cancer or cervical cancer in situ;

B. Presence of distant metastasis;

C. Presence of mental disease or psychotic manifestation;

D. Active or uncontrolled infection;

E. Significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications at physician discretion

F. Pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential.

G. History of active autoimmune disease within 3 years or use of steroid more than prednisolone 10mg/day.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SLOG	Drug: S-1, leucovorin, oxaliplatin and gemcitabine; Gemcitabine 800 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, S-1 orally 80-120 mg/day [depending on patient's body surface area (BSA)] on day 1 to 7 and leucovorin 30mg BID day 1 to 7 on in a 2-week cycle. The dose of S-1 is defined as follows: BSA < 1.25 m2: 80 mg/day; 1.25 m2 ≤ BSA < 1.5 m2: 100 mg/day; BSA ≥ 1.5 m2: 120 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of subjects with R0 resection after surgery	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		2 years
The percentage of subjects successfully underwent surgery after study drug treatment		1 year
The percentage of subjects with tumor shrinkage >30%	according to RECIST 1.1	1 year
The percentage of subjects without tumor progression	tumor progression is defined as increase of size by >20% according to RECIST 1.1	1 year
Progression-free survival (PFS) of patient received study treatment		1 year
Overall survival (OS) of patient received study treatment		2 years
Duration of response (DOR) of patient received study treatment		1 year
Biomarkers of treatment response by single cell RNA sequencing and whole exome sequencing	Biomarkers including but not limited to tumor mutation burden, change of immune cell proportion and percentage of T-reg in the tumor microenvironment.	4 years

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Estimated): August 24, 2024
• Study Completion (Estimated): August 24, 2025

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 8, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; S-1; Neoadjuvant Therapy; Oxaliplatin; Leucovorin; SLOG
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Oxaliplatin; Leucovorin; Gemcitabine
• Other Study ID Numbers: SLOG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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