Concurrent and Adjuvant PD1 Treatment Combined With Chemo-radiotherapy for High-risk Nasopharyngeal Carcinoma

Phase 3

Recruiting

• Conditions: Nasopharyngeal Cancer; Radiotherapy; PD-1 Therapy; Chemotherapy
• Interventions: Drug: Chemo-radiotherapy alone; Drug: Camrelizumab plus chemo-radiotherapy

• Registration Number: NCT04453826
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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

Detailed Description

Through multicenter, open-label, randomised clinical trials, high risk patients with nasopharyngeal carcinoma (staged as II-III with SD/PD according to RECIST criteria or EBV DNA of \>0 copies/mL after 3 cycles of GP induction chemotherapy and staged as IVa) are randomized into camrelizumab plus chemo-radiotherapy arm and chemo-radiotherapy arm. The efficacy and safety of patients between these two arms are compared.

Study Timeline

• Study First Submitted: 2020-06-27
• Study First Submitted QC: 2020-06-27
• Study First Posted: 2020-07-01
• Status Verified: 2020-09
• Study Start: 2020-09-01
• Last Update Submitted: 2020-09-24
• Last Update Posted: 2020-09-28
• Primary Completion: 2026-09
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 388

Inclusion Criteria

1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).

2. Staged as T4N0-2M0,T1-4N3M0 (stage IVa) at diagnosis (according to the 8th AJCC edition).

3. Staged as T1-3N1-2M0, T2-3N0M0 (stage II-III) with SD/PD according to RECIST criteria or EBV DNA of >0 copies/mL after 3 cycles of GP induction chemotherapy.

4. Aged between 18-70 years.

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. Histologically confirmed keratinized squamous cell carcinoma (WHO type I) or basal squamous cell carcinoma.
2. Recurrent or metastatic nasopharyngeal carcinoma.
3. Staged as II-III which is evaluated as PR or CR and EBV DNA of 0 copies/mL after 3 cycles of GP induction chemotherapy.
4. Has known allergy to large molecule protein products or any compound of study therapy.
5. Has known subjects with other malignant tumors.
6. Has any active autoimmune disease or history of autoimmune disease.
7. Has a history of psychiatric substance abuse, alcoholism, or drug addiction.
8. The laboratory examination value does not meet the relevant standards within 7 days before enrollment
9. Received a systematic glucocorticoid therapy within 4 weeks of the first dose of study medication.
10. Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB with 1 year.
11. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.
12. 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.
13. Has a known history of human immunodeficiency virus (HIV).
14. Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of ≥1000cps/ml or hepatitis C virus (HCV) antibody positive.
15. Has received a live vaccine within 4 weeks of planned start of study therapy.
16. Pregnancy or breast feeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemo-radiotherapy arm	Chemo-radiotherapy alone	3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent chemo-radiotherapy.
Camrelizumab plus chemo-radiotherapy arm	Camrelizumab plus chemo-radiotherapy	3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent chemo-radiotherapy with concurrent and adjuvant camrelizumab therapy.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

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, 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