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

Nasopharyngeal Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04453813
• Other study ID #: SYSUCC-MYC-2020-2101
• Status: Recruiting
• Phase: Phase 3
• Start date: July 3, 2020
• Est. completion date: July 2027

Study information

• Verified date: September 2020
• Source: Sun Yat-sen University
• Contact: Ming-Yuan Chen, MD, PhD
• Phone: : 86-20-87343624
• Email: chmingy[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 226
• Est. completion date: July 2027
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Chemotherapy
• Nasopharyngeal Carcinoma
• PD-1 Treatment
• Radiotherapy

Intervention

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
• 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

Locations

Country	Name	City	State
China	Cancer Center of Guangzhou Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Yuebei People's Hospital	Shaoguan	Guangdong
China	Wuzhou Red Cross Hospital	Wuzhou	Guangxi
China	Zhongshan People's Hospital	Zhongshan	Guangdong
China	The Fifth Affiliated Hospital of Sun Yat-sen University	Zhuhai	Guangdong

Sponsors (6)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	Defined as the time interval from randomization to death due to any cause.	3 years
Secondary	Distant Metastasis-Free Survival (DMFS)	Defined as the time interval from randomisation to the date of first distant metastases.	3 years
Secondary	Locoregional Relapse-Free Survival (LRRFS)	Defined as the time from randomisation to the date of first locoregional relapse.	3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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