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

A Multicenter Randomized Clinical Phase 3 Trial of Induction Chemotherapy Plus Concurrent Chemo-radiotherapy With or Without Camrelizumab for High Risk Nasopharyngeal Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Cancer; Chemotherapy; Radiotherapy; PD-1 Therapy
• Intervention / Treatment: Drug: Camrelizumab plus chemo-radiotherapy; Drug: 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 Type: Interventional
• Enrollment (Anticipated): 388
• 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
      • Recruiting
      • Zhongshan People's Hospital
      • Contact: Feng Lei, MD; Email: 13528227676@163.com
      • Principal Investigator: Feng Lei, MD
    • Zhuhai, Guangdong, China, 519000
      • 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
      • Not yet 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 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 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: Camrelizumab plus chemo-radiotherapy arm; 3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent chemo-radiotherapy with concurrent and adjuvant camrelizumab therapy.	Drug: Camrelizumab plus chemo-radiotherapy; Camrelizumab: 200 mg, intravenous injection over 60 minutes (Q3W); 2 cycles of camrelizumab are concurrently used during radiotherapy and camrelizumab are maintained for 1 year after the end of radiotherapy.; Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks.; 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#69.96Gy/33Fr/2.12Gy; PTVnd#69.96Gy/33Fr/2.12Gy; PTV1#59.4Gy/33Fr/1.8Gy; PTV2#54Gy/33Fr/1.64Gy
Active Comparator: Chemo-radiotherapy arm; 3 cycles of gemcitabin and cisplatin induction chemotherapy plus concurrent chemo-radiotherapy.	Drug: Chemo-radiotherapy alone; Gemcitabine plus cisplatin induction chemotherapy: gemcitabine is injected intravenously at the dose of 1000 mg/m2 on the 1st and 8th day (within 30 minutes) for 3 cycles; cisplatin is injected intravenously at the dose of 80 mg/m2 on the 1st day, for 3 cycles. 1 cycles per 3 weeks.; 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#69.96Gy/33Fr/2.12Gy; PTVnd#69.96Gy/33Fr/2.12Gy; PTV1#59.4Gy/33Fr/1.8Gy; PTV2#54Gy/33Fr/1.64Gy

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): September 1, 2020
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): September 1, 2028

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; Carcinoma; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
• Other Study ID Numbers: SYSUCC-MYC-2020-1103

Drug and device information, study documents

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