Programmed Death-1 (PD-1) Antibody Combined With Chemoradiotherapy in High-risk Recurrent Nasopharyngeal Carcinoma

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03930498

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a a prospective, single-arm phase II clinical trial. The purpose of this study is to evaluate the efficacy and adverse effect of PD-1 antibody with chemotherapy in high-risk recurrent nasopharyngeal carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Nasopharyngeal Carcinoma	Drug: PD-1 blocking antibody Drug: Chemotherapy Radiation: IMRT	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

68 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

PD-1 Antibody Combined With Chemotherapy in High-risk Recurrent Nasopharyngeal Carcinoma: a Prospective, Open, Single-arm Phase II Clinical Trial

Actual Study Start Date :

Mar 1, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-1 antibody plus chemoradiotherapy	Drug: PD-1 blocking antibody Toripalimab is an antibody targeting PD-1 developed by Shanghai Junshi Biosciences Co., Ltd. Other Names: JS001 Drug: Chemotherapy Cisplatin and Gemcitabine Radiation: IMRT IMRT 60-66Gy, 1.8-2.0Gy/f/day

Arm

Intervention/Treatment

Experimental: PD-1 antibody plus chemoradiotherapy

Drug: PD-1 blocking antibody

Toripalimab is an antibody targeting PD-1 developed by Shanghai Junshi Biosciences Co., Ltd.

Other Names:

JS001

Drug: Chemotherapy

Cisplatin and Gemcitabine

Radiation: IMRT

IMRT 60-66Gy, 1.8-2.0Gy/f/day

Outcome Measures

Primary Outcome Measures

Overall survival [2 years]
From date of recruitment to death

Secondary Outcome Measures

Objective response rate [After 3 cycles of GP chemothrapy plus PD-1 antibody (each cycle is 21 days)]
Patient's short-term effect
Disease control rate [After 3 cycles of GP chemothrapy plus PD-1 antibody (each cycle is 21 days)]
Patient's short-term effect
Progression free survival [2 years]
From date of recruitment to disease progression or death
Adverse effects [through study completion, an average of 3 months]
Evaluating with CTCAE v5.0
Quality of life: EuroQoL 5 dimension [through whole study, an average of 2 years]
Evaluating with questionnaire of EuroQoL 5 dimension, 5 level health state utility index (EQ-5D-5L)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment;
Not suitable for surgery;
Newly histologic diagnosis of NPC (WHO II/III);
Clinical stage rII-IVa (AJCC/UICC 8th);
ECOG 0-1 point;
PRANCIS score > 252 points;
No treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
No contraindications to immunotherapy or chemoradiotherapy;
Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
Take effective contraceptions during and two months after treatment;
Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

Have recurrence with local necrosis;
Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
Unexplained fever > 38.5 ℃, except for tumor fever;
Treated with ≥ 5 days antibiotics one month before enrollment;
Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy);
Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive;
Have previously treated with PD-1 antibody or other immunotherapy for PD-1/PD-L1 pathway;
Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
Have known allergy to large molecule protein products or any compound of study therapy;
Pregnant or breastfeeding;
Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
Have received a live vaccine within 30 days of planned start of study therapy Has psychiatric drug or substance abuse disorders that would interfere with cooperation with the requirements of the trial;
Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.