Chemoradiotherapy Plus Anti-PD1 in Recurrent NPC: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Official title

Chemoradiotherapy Combined With Programmed Death 1 Antibody in Recurrent Nasopharyngeal Carcinoma: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Overview

This is a multicenter, open-label, randomized, controlled, phase III trial. The purpose of this trial is to evaluate the efficacy and toxicity of anti-PD-1 antibody combined with chemoradiotherapy versus chemoradiotherapy alone in recurrent nasopharyngeal carcinoma patients.

Interventions

• Drug Toripalimab
  240mg, D1, every 3 weeks per cycle, three cycles with chemotherapy and eight cycles after IMRT
• Drug Chemotherapy
  Gemcitabine: 1.0g/m2, D1 and D8, Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles
• Radiation Intensity modulated radiotherapy
  total 60-66Gy, 1.8-2.0Gy/f/day

Primary outcome measures

• Overall survival [Time frame: three years]

Secondary outcome measures (7)

• Failure-free survival [Time frame: three years]
• Objective response rate through study completion, an average of nine months [Time frame: through study completion, an average of nine months]
• Disease control rate through study completion, an average of nine months [Time frame: through study completion, an average of nine months]
• Incidence of nasopharyngeal necrosis and hemorrhage up to 3 years [Time frame: up to three-year follow-up]
• Acute toxicities were graded using the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0) [Time frame: through study completion, an average of nine months]
• Late toxicity [Time frame: three years]
• Quality of life through study completion, up to 3 years [Time frame: up to three-year follow-up]

Eligibility criteria

Inclusion criteria

• Diagnosed as local with or without regional recurrence after ≥1 year of radical treatment;
• Not suitable for surgery;
• Histologic diagnosis of NPC (WHO II/III);
• TNM stage rII-IVa (AJCC/UICC 8th);
• ECOG 0-1 point;
• No treatment to rNPC prior, 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

• 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 ≥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.

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: NCT05340491 · B2022-111-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗