Nimotuzumab Plus S1 Versus Placebo Plus S1 as Maintenance Treatment in Patients With Unresectable Pancreatic Cancer

A Randomized, Controlled, Double Blind, Multicenter Study of Nimotuzumab Plus S1 Versus Placebo Plus S1 as Maintenance Treatment in Patients With Advanced or Metastatic Pancreatic Cancer After First-line Treatment

Background: Monotherapy with S-1, oral fluoropyrimidine, shows non-inferiority to gemcitabine in overall survival (OS) with good tolerability for advanced pancreatic cancer in Asian patients. It is also shown that nimotuzumab plus gemcitabine could improve OS and progression free survival (PFS) in patients with unresectable pancreatic cancer. However, it is still unknown whether nimotuzumab plus S1 would improve more to OS and PFS than single S-1. Maintenance treatment, as a new treatment pattern, has also been tried in these patients after first line treatment to improve the OS. Thus, this study is designed to compare nimotuzumab plus S1 to placebo plus S1 as maintenance treatment in patients with locally advanced or metastatic pancreatic cancer who has benefited from the first-line treatment of gemcitabine combined with nimotuzumab and S1 (complete response+partial response+stable disease).

Patients and methods: 60 patients will be enrolled,and randomized in a 1:1 ratio to group nimotuzumab plus S1 and group placebo plus S1. nimotuzumab/placebo: 400 mg/w, intravenous infusion, Infusion time ≥ 60 min, d1, once every two weeks. S1: oral, 40 mg (Body surface area<1.5 m2) or 60 mg (Body surface area>1.5 m2), d1-d14, every three weeks for a cycle. Treatment interventions will be stopped under the conditions of disease progression or intolerable toxic reaction or participants ask to quit. The primary endpoint is the time to disease progression since randomization (TTP), secondary points include OS, 3 years overall survival rate (OSR) and safety.

Study Overview

• Status: Unknown
• Conditions: Unresectable Pancreatic Cancer
• Intervention / Treatment: Drug: Nimotuzumab plus S1; Drug: Placebo plus S1

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100853
    • Chinese PLA General Hospital
  • Beijing, China, 100730
    • Beijing Hospital
  • Beijing, China, 100142
    • Air Force General Hospital, PLA
  • Beijing, China, 100021
    • Cancer Hospital Chinese Academy of Medical Sciences
  • Beijing, China, 100048
    • First Affiliated Hospital of PLA General Hospital
  • Beijing, China, 100088
    • Rocket Army General Hospital, PLA
  • Beijing, China, 100101
    • The 306th Hospital of PLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-75 years;
• Karnofsky Performance Status≥ 60;
• histologically proven locally advanced or metastatic pancreatic cancer,and unsuitable for radiotherapy or surgery resection;
• benefited from the first line treatment of gemcitabine plus nimotuzumab and S1 (complete response+partial response+stable disease);
• at least 4 weeks from the end of the first-line treatment;
• with at least 1 measurable and evaluable lesion;
• anticipated over survival≥12 weeks;
• AST/ALT≤2.5 ULN (≤5 ULN for patients with hepatic metastases); total bilirubin≤2 ULN （≤3 ULN for patients with hepatic metastases); neutrophil count≥1.5×109/L; platelet counts≥100×109/L; hemoglobin level≥90 g/L; creatinine clearance rate≥ 60 mL/min
• written informed consent

Exclusion Criteria:

• previously received the following treatments: anticancer chemotherapy/molecularly targeted therapy as palliative treatment, or targeted chemotherapy and no progression, another interventional clinical trail within 4 weeks;
• underwent major surgery within 4 weeks;
• with brain or leptomeningeal metastases;
• history of malignancy other than pancreatic cancer;
• presented symptomatic abdominal fluid and needed treatment;
• with other serious diseases such as diabetes,active infection;
• known for allergy to anti epidermal growth factor receptor antibody

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nimotuzumab plus S1; Nimotuzumab Injection:400 mg/w, Intravenous infusion, Infusion time ≥ 60 min, d1, once every two weeks; S1:40 mg (Body surface area<1.5 m2) or 60mg (Body surface area>1.5 m2) ,oral,d1-d14, every three weeks for a cycle	Drug: Nimotuzumab plus S1; Nimotuzumab Injection: 400 mg/w, Intravenous infusion, Infusion time ≥ 60 min, d1, once every two weeks;S1: 40 mg (Body surface area<1.5 m2) or 60 mg (Body surface area>1.5 m2) ,oral,d1-d14, every three weeks for a cycle; Other Names: Taixinsheng，Tegafur Gimeracil Oteracil Potassium Capsule
ACTIVE_COMPARATOR: Placebo plus S1; Placebo:400 mg/w, Intravenous infusion, Infusion time ≥ 60 min, d1, once every two weeks; S1:40 mg (Body surface area<1.5 m2) or 60 mg (Body surface area>1.5 m2) ,oral,d1-d14, every three weeks for a cycle	Drug: Placebo plus S1; Placebo: 400 mg/w, Intravenous infusion, Infusion time ≥ 60 min, d1, once every two weeks;S1: 40 mg (Body surface area<1.5 m2) or 60 mg (Body surface area>1.5 m2) ,oral,d1-d14, every three weeks for a cycle; Other Names: Tegafur Gimeracil Oteracil Potassium Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
TTP	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
OS	3 years
OSR	1-3 years
Adverse Events	3 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Yi Hu, PhD, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (ESTIMATE): October 26, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Unresectable; Maintenance Treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab; Tegafur
• Other Study ID Numbers: PC20150423

Plan for Individual participant data (IPD)

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