PD-1 Antibody Versus Best Supportive Care After Chemoradiation in Locoregionally Advanced Nasopharyngeal Carcinoma (DIPPER)

Camrelizumab (PD-1 Antibody) Compared With Best Supportive Care After Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: a Multi-center, Randomised Controlled, Phase 3 Trial (DIPPER)

This trial is aimed to investigate whether adjuvant PD-1 antibody treatment could improve survival in locoregionally advanced nasopharyngeal carcinoma compared to best supportive care.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Neoplasms
• Intervention / Treatment: Drug: Camrelizumab

Detailed Description

In this multicenter, randomised controlled, phase 3 trial, patients with stage III-IVA (AJCC/UICC 8th system, except T3-4N0 and T3N1) non-metastatic nasopharyngeal carcinoma will be randomized in a 1:1 ratio to recieve PD-1 antibody for 12 doses every 3 weeks or best supportive care after curative chemoradiation.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jun Ma, MD; Phone Number: +862087343469; Email: majun@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China
      • First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510060
      • Panyu Central Hospital
    • Guangzhou, Guangdong, China, 510060
      • Guangzhou Medical University Cancer Hospital
  • Guangxi
    • Nanning, Guangxi, China
      • Cancer Hospital of Guangxi Medical University
  • Guizhou
    • Guiyang, Guizhou, China
      • Cancer Hospital of Guizhou Medical University
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China
      • Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Hospital Central South University
  • Shanxi
    • Xi'an, Shanxi, China
      • Xijing Hospital, Fourth Military Medical University
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histologically confirmed nasopharyngeal carcinoma.
• Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
• Completed protocol-specified curative chemoradiotherapy, including gemcitabine and cisplatin induction chemotherapy, intensity-modulated radiotherapy, and concurrent cisplatin chemotherapy.
• Completion of the last radiation dose within 1 to 42 days before randomization
• Eastern Cooperative Oncology Group performance status ≤1.
• Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
• Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
• Patients must be informed of the investigational nature of this study and give written informed consent.
• Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug.

Exclusion Criteria:

• Age > 65 or < 18.
• Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 copies/ml or 200IU/ml
• Hepatitis C virus (HCV) antibody positive
• Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
• Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
• Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.
• Has a known history of interstitial lung disease.
• Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
• Is pregnant or breastfeeding.
• Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
• Has known allergy to large molecule protein products or any compound of camrelizumab.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

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: Adjuvant PD-1 antibody arm; Patients randomized to this arm will receive PD-1 antibody (SHR-1210), 200mg, ivdrip (>30 minutes), d1, q3w × 12 cycles, begining at 4-6 weeks after chemoradiation	Drug: Camrelizumab; Camrelizumab is an antibody targeting PD-1 developed by Jiangsu Hengrui Medicine, China.; Other Names: SHR-1210
No Intervention: Best supportive care; Patients randomized to this arm will receive best supportive care after chemoradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
failure-free survival	calculated from the date of randomisation to the date of locoregional failure, distant failure, or death from any cause, whichever occurred first.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	calculated from date of randomisation to death	5 years
distant metastasis-free survival	calculated from date of randomisation to the first distant failure	3 years
locoregional recurrence-free survival	calculated from date of randomisation to the first locoregional failure	3 years
adverse events (AEs) and severe adverse events (SAE)	graded according to NCI CTCAE v5.0	3 years
quality of life (QoL)	the change of QoL from randomization to 36 months after chemoradiation, graded according to EORTC QLQ-C30 V3.0	3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jun Ma, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2018
• Primary Completion (Actual): February 6, 2024
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 3, 2018
• First Submitted That Met QC Criteria: February 3, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Adjuvant treatment; Immune checkpoint inhibitors; PD-1 antibody
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
• Other Study ID Numbers: B2017-097-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Complete de-identified patient data set
• IPD Sharing Time Frame: For 2 years started from 12 months after publication of the primary trial report.
• IPD Sharing Access Criteria: Authoritative researchers who provide a methodologically sound proposal for individual participant data meta-analysis.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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