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

Official title

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

Overview

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.

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.

Interventions

• Drug Toripalimab plus concurrent chemo-radiotherapy
  1. 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). 2. 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. 3. IMRT: PTVnx#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/2
• Drug Concurrent chemo-radiotherapy
  1. 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. 2. IMRT: PTVnx#60.0Gy/27Fr/2.22Gy; PTVnd# 60-64Gy/27Fr/2.22-2.37Gy; PTV1#54Gy/27Fr/2.00Gy

Primary outcome measures

• Progress-free survival (PFS) [Time frame: 3 years]

Secondary outcome measures (7)

• Overall Survival (OS) [Time frame: 3 years]
• Distant Metastasis-Free Survival (DMFS) [Time frame: 3 years]
• Locoregional Relapse-Free Survival (LRRFS) [Time frame: 3 years]
• Incidence of treatment related acute complications [Time frame: up to 1 years]
• Incidence of treatment related late complications [Time frame: up to 3 years]
• Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) [Time frame: up to 3 years]
• Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) [Time frame: up to 3 years]

Eligibility criteria

Inclusion criteria

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

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

Exclusion criteria

• 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).
• 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.
• Has known allergy to large molecule protein products or any compound of study therapy.
• Has known subjects with other malignant tumors.
• Has any active autoimmune disease or history of autoimmune disease.
• Has a history of psychiatric substance abuse, alcoholism, or drug addiction.
• The laboratory examination value does not meet the relevant standards within 7 days before enrollment
• Received a systematic glucocorticoid therapy within 4 weeks of the first dose of study medication.
• Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB with 1 year.
• Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.
• 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.
• Has a known history of human immunodeficiency virus (HIV).
• Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive
• Has received a live vaccine within 4 weeks of planned start of study therapy
• Pregnancy or breast feeding

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

• Sun Yat-sen University Cancer Center — Guangzhou
• Cancer Center of Guangzhou Medical University — Guangzhou
• Yuebei People's Hospital — Shaoguan
• Zhongshan People's Hospital — Zhongshan
• The Fifth Affiliated Hospital of Sun Yat-sen University — Zhuhai
• Wuzhou Red Cross Hospital — Wuzhou

Identifiers

NCT: NCT04453813 · SYSUCC-MYC-2020-2101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗