Clinical trial NCT04453813: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Carcinoma
Chemotherapy
Radiotherapy
PD-1 Treatment
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Zhongshan People's Hospital, Guangdong, China
name: Yuebei People's Hospital
name: Wuzhou Red Cross Hospital
name: Fifth Affiliated Hospital, Sun Yat-Sen University
First posted: 2020-07-01
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progress-free survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 3 years
measure: Locoregional Relapse-Free Survival (LRRFS)
timeFrame: 3 years
measure: Incidence of treatment related acute complications
timeFrame: up to 1 years
measure: Incidence of treatment related late complications
timeFrame: up to 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
timeFrame: up to 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Wuzhou
country: China
facility: Wuzhou Red Cross Hospital
state: Guangxi
Study officials:
References: