Toripalimab Plus Concurrent Chemo-radiotherapy for Unresectable Locally Recurrent Nasopharyngeal Carcinoma

A Multicenter Randomized Clinical Phase 3 Trial of Toripalimab Plus Concurrent Chemo-radiotherapy vs Concurrent Chemo-radiotherapy Alone for Unresectable Locally Recurrent Nasopharyngeal Carcinoma

Through multicenter, open-label, randomised clinical trials, we intend to demonstrate that concurrent and adjuvant PD-1 treatment added to concurrent chemo-radiotherapy could further decrease the rate of disease progression and improve the survival outcome of patients with unresectable locally recurrent nasopharyngeal carcinoma compared with those treated with concurrent chemo-radiotherapy alone.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma; Chemotherapy; Radiotherapy; PD-1 Treatment
• Intervention / Treatment: Drug: Toripalimab plus concurrent chemo-radiotherapy; Drug: Concurrent chemo-radiotherapy

Detailed Description

Through multicenter, open-label, randomised clinical trials, patients with unresectable locally recurrent nasopharyngeal carcinoma are randomized into concurrent chemo-radiotherapy plus concurrent and adjuvant PD-1 treatment group and concurrent chemo-radiotherapy alone group. The efficacy and safety of patients between these two groups are compared.

• Study Type: Interventional
• Enrollment (Anticipated): 226
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ming-Yuan Chen, MD, PhD; Phone Number: : 86-20-87343624; Email: chmingy@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510095
      • Not yet recruiting
      • Cancer Center of Guangzhou Medical University
      • Contact: Dong-Ping Chen, MD; Phone Number: 86-13302215492; Email: chen_dpgz@163.com
      • Principal Investigator: Dong-Ping Chen, MD
    • Shaoguan, Guangdong, China, 512025
      • Not yet recruiting
      • Yuebei People's Hospital
      • Contact: Su-Ming Pan, MD; Phone Number: 86-13826331948
      • Principal Investigator: Su-Ming Pan, MD
    • Zhongshan, Guangdong, China, 528403
      • Not yet recruiting
      • Zhongshan People's Hospital
      • Principal Investigator: Feng Lei, MD
      • Contact: Feng Lei, MD; Phone Number: 86-18933345382; Email: 13528227676@163.com
    • Zhuhai, Guangdong, China, 519000
      • Not yet recruiting
      • The Fifth Affiliated Hospital of Sun Yat-sen University
      • Contact: Zhi-Gang Liu, MD, PhD; Phone Number: 86-18627585860
      • Principal Investigator: Zhi-Gang Liu, MD, PhD
  • Guangxi
    • Wuzhou, Guangxi, China, 543002
      • Recruiting
      • Wuzhou Red Cross Hospital
      • Contact: Jin-Hui Liang, MD; Phone Number: 86-13878480806
      • Principal Investigator: Jin-Hui Liang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed recurrent nasopharyngeal carcinoma.
2. The recurrence time is more than 12 months from the end of the first course of radiotherapy.
3. Tumor staged as rT2-4N0-3M0，rII-IVa (according to the 8th AJCC edition).
4. Subjects must have a measurable disease by CT or MRI per RECIST 1.1 criteria.
5. Karnofsky scale (KPS)≥70.
6. Normal bone marrow function.

7. Normal liver and kidney function:

   1. total bilirubin, AST and ALT levels of no more than 2.5 times the upper normal limit;
   2. creatinine clearance rate of at least 60 mL/min or creatinine of no more than 1.5 times the upper normal limit.
8. Given written informed consent.

Exclusion Criteria:

1. Resectable nasopharyngeal diseases: rT2 (the tumour is confined in the superficial parapharyngeal spacer and is more than 0.5cm from the internal carotid artery) and rT3 (the tumour is confined in the base wall of the sphenoid sinus and is more than 0.5cm from the internal carotid artery and cavernous sinus).
2. The patients are suffering from severe nasopharyngeal necrosis, radiation induced brain injury, and fibrosis of the neck et. al, who are evaluated as unsuitable for secondary radiotherapy by the researchers.
3. Has known allergy to large molecule protein products or any compound of study therapy.
4. Has known subjects with other malignant tumors.
5. Has any active autoimmune disease or history of autoimmune disease.
6. Has a history of psychiatric substance abuse, alcoholism, or drug addiction.
7. The laboratory examination value does not meet the relevant standards within 7 days before enrollment
8. Received a systematic glucocorticoid therapy within 4 weeks of the first dose of study medication.
9. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB with 1 year.
10. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.
11. Has active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy). Patients with skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) will be allowed to enroll.
12. Has a known history of human immunodeficiency virus (HIV).
13. Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive
14. Has received a live vaccine within 4 weeks of planned start of study therapy
15. Pregnancy or breast feeding

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: Toripalimab plus concurrent chemo-radiotherapy arm; Concurrent chemo-radiotherapy plus concurrent and adjuvant toripalimab.	Drug: Toripalimab plus concurrent chemo-radiotherapy; Toripalimab: 240 mg, intravenous injection over 60 minutes (Q3W); 2 cycles of toripalimab are concurrently used during radiotherapy and other 9 cycles of toripalimab are used after the end of radiotherapy. (A total of 11 cycles).; Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks.; IMRT: PTVnx#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy
Active Comparator: Concurrent chemo-radiotherapy arm; Concurrent chemo-radiotherapy alone.	Drug: Concurrent chemo-radiotherapy; Concurrent cisplatin chemotherapy: cisplatin is given at a dose of 100 mg/m2 via a continuous intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy for 2 cycles. 1 cycles per 3 weeks.; IMRT: PTVnx#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress-free survival (PFS)	Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Defined as the time interval from randomization to death due to any cause.	3 years
Distant Metastasis-Free Survival (DMFS)	Defined as the time interval from randomisation to the date of first distant metastases.	3 years
Locoregional Relapse-Free Survival (LRRFS)	Defined as the time from randomisation to the date of first locoregional relapse.	3 years
Incidence of treatment related acute complications	The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria.	up to 1 years
Incidence of treatment related late complications	The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria.	up to 3 years
Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)	Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment.	up to 3 years
Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)	Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment.	up to 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Wuzhou Red Cross Hospital; Fifth Affiliated Hospital, Sun Yat-Sen University; Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Zhongshan People's Hospital, Guangdong, China; Yuebei People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2020
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): July 1, 2027

Study Registration Dates

• First Submitted: June 27, 2020
• First Submitted That Met QC Criteria: June 27, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: SYSUCC-MYC-2020-2101

Drug and device information, study documents

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