PD-1 Antibody Combined With Chemoradiotherapy in Recurrent Nasopharyngeal Carcinoma Patients

Official title

PD-1 Antibody Combined With Chemoradiotheapy vs. Chemoradiotherapy in Recurrent Nasopharyngeal Carcinoma Patients: a Multicenter, Randomised Controlled, Phase III Clinical Trial

Overview

This is a multicenter, randomized controlled, phase III clinical trial. The purpose of this study is to evaluate the efficacy and adverse effect of PD-1 antibody with chemoradiotherapy versus chemoradiotherapy alone in recurrent nasopharyngeal carcinoma patients.

Interventions

• Drug PD-1 blocking antibody
  Toripalimab 240mg, D1, every 3 weeks per cycle
• Drug GP
  Gemcitabine 1.0g/m2, D1 and D8; Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles
• Radiation IMRT
  IMRT 60-66Gy, 1.8-2.0Gy/f/day

Primary outcome measures

• Overall survival [Time frame: 3 years]

Secondary outcome measures (4)

• Progression free survival [Time frame: 3 years]
• Short-term effects [Time frame: through study completion, an average of 2 months]
• Rate of patients with acute toxicities [Time frame: through study completion, an average of 2 months]
• Quality of life: EuroQoL 5 dimension [Time frame: through whole study, an average of 3 years]

Eligibility criteria

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;
• No treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
• No contraindications to immunotherapy or radiotherapy;
• 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

• Treated with anti-tumor Chinese medicine treatment;
• 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 ≥10E4copiers/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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 12 centers

• Sun Yat-sen University Cancer Center — Guangzhou
• Peking University Third Hospital — Beijing
• Sichuan Cancer Hospital — Chengdu
• Fujian Province Cancer Hospital — Fuzhou
• Guizhou Cancer Hospital — Guiyang
• Zhejiang Cancer Hospital — Hangzhou
• Jiangxi Cancer Hospital — Nanchang
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• … and 4 more centers

Identifiers

NCT: NCT03907826 · rNPC-JS001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗