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

Radiotherapy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04453826
• Other study ID #: SYSUCC-MYC-2020-1103
• Status: Recruiting
• Phase: Phase 3
• Start date: September 1, 2020
• Est. completion date: September 2028

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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 388
• Est. completion date: September 2028
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chemotherapy
• Nasopharyngeal Cancer
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms
• PD-1 Therapy
• Radiotherapy

Intervention

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
• 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

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