Clinical trial NCT04453826: Concurrent and Adjuvant PD1 Treatment Combined With Chemo-radiotherapy for High-risk Nasopharyngeal Carcinoma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nasopharyngeal Cancer
Chemotherapy
Radiotherapy
PD-1 Therapy
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: 388
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 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.

Eligibility criteria: 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.

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: