40.2Gy Versus 49.2Gy Radiotherapy in Low-Risk Target Volume for Chemosensitive Stage II Nasopharyngeal Carcinoma

Official title

40.2Gy Versus 49.2Gy Radiotherapy in Low-Risk Target Volume for Chemosensitive Stage II Nasopharyngeal Carcinoma Under Full-Course Immunotherapy: a Multicentre, Randomised, Phase 3 Trial

Overview

This study aims to explore the efficacy and adverse events of reduced-dose radiotherapy (40.2Gy) versus conventional-dose radiotherapy (49.2Gy) to low-risk target volume for chemosensitive intermediate-stage nasopharyngeal carcinoma patients.

Detailed description

This study intends to enroll low-risk intermediate-stage nasopharyngeal carcinoma patients who achieve CR/PR after induction chemotherapy and whose plasma EBV-DNA level has dropped to 0 or below the lower detection limit. These patients will be randomly assigned at a 1:1 ratio to receive either reduced-dose radiotherapy (40.2Gy) or conventional-dose radiotherapy (49.2Gy) to CTV2. Both groups will receive full-course immunotherapy. The study will follow up to observe differences in survival, adverse events, and quality of life between the two groups. It is expected that, on the premise of maintaining treatment efficacy, reducing the dose to CTV2 can decrease acute and chronic toxicities caused by radiotherapy and chemotherapy, thereby improving patients' quality of life.

Interventions

• Drug Cisplatin-based induction chemotherapy
  Gemcitabine + cisplatin: Gemcitabine, 1,000 mg/m², Q3W, d1+d8, IV drip; cisplatin, 80 mg/m², Q3W, d1-3, IV drip. A total of 3 cycles. (Note: Gemcitabine can be replaced by docetaxel, albumin-bound paclitaxel, paclitaxel, etc.)
• Drug Full course of PD-1 monoclonal antibody
  Tislelizumab 200 mg , once every 3 weeks (Q3W), intravenous infusion (iv). A total of 12 courses of treatment will be administered, including 3 courses during the induction chemotherapy phase, 3 courses during the radiotherapy phase, and 6 courses during the post-radiotherapy maintenance phase. Administration will start on Day 1 of induction chemotherapy and continue after the end of radiotherapy until the occurrence of intolerable toxicities, disease progression, withdrawal of consent, determin
• Radiation Reduced-dose radiotherapy to CTV2
  GTV, 63.6Gy/30Fr/2.12Gy; CTV1, 54Gy/30Fr/1.8Gy; CTV2, 40.2Gy/30F/1.34Gy
• Radiation Conventional-dose radiotherapy to CTV2
  GTV, 63.6Gy/30Fr/2.12Gy; CTV1, 54Gy/30Fr/1.8Gy; CTV2, 49.2Gy/30Fr/1.64Gy

Primary outcome measures

• Progress-Free Survival (PFS) [Time frame: 3 years]
• Incidence of ≥3 grade adverse events [Time frame: 3 years]

Secondary outcome measures (6)

• Distant Metastasis-Free Survival (DMFS) [Time frame: 3 years]
• Locoregional Relapse-Free Survival (LRRFS) [Time frame: 3 years]
• Overall Survival (OS) [Time frame: 3 years]
• Objective Response Rate (ORR) [Time frame: 3 months]
• Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) [Time frame: 3 years]
• Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Patients are informed of the basic content of this study and sign an informed consent form;
• Age between 18 and 75 years;
• Pathologically diagnosed as non-keratinising nasopharyngeal carcinoma (differentiated or undifferentiated, i.e., WHO type II or III);
• Staged according to the 9th edition of the AJCC/UICC TNM classification as T1-3N2M0 or T3N0-1M0 (Stage II);
• KPS ≥ 70;
• Normal bone marrow function: WBC ≥ 4 × 10⁹/L, PLT ≥ 100 × 10⁹/L, HGB ≥ 90 g/L;
• Imaging evaluation of treatment response after three cycles of GPP/TPP induction chemotherapy plus immunotherapy: CR or PR;
• Plasma EBV DNA level decreases to 0 copies/mL or below the detection limit after induction chemotherapy;
• Normal liver and kidney function: total bilirubin, AST, ALT ≤ 2.0 times the upper limit of normal, creatinine clearance ≥ 60 mL/min or creatinine ≤ 1.5 times the upper limit of normal.

Exclusion criteria

• Patients with recurrent/metastatic nasopharyngeal carcinoma;
• Pregnant or breastfeeding women (pregnancy tests should be considered for women of childbearing age; effective contraception should be emphasised during treatment);
• Patients with a history of malignant tumours, excluding those who have undergone curative treatment for cervical cancer, basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer, or ductal carcinoma in situ;
• Patients whose local/regional lesions have undergone radiotherapy or surgery (excluding diagnostic surgery), or whose lesions exhibit significant necrosis, making radiotherapy unsuitable or potentially leading to radiotherapy resistance;
• Patients with other severe medical conditions that may pose significant risks or impair trial compliance. Examples include unstable cardiac disease requiring treatment, renal disease, hepatic disease, uncontrolled diabetes (fasting blood glucose > 1.5 × ULN), severe psychiatric disorders, or other malignant tumours;
• Patients with a history of severe hypersensitivity reactions to any component of PD-1 monoclonal antibodies;
• History of allergic reactions to the chemotherapy drugs used in this study (gemcitabine, docetaxel, albumin-bound paclitaxel, paclitaxel, cisplatin);
• Patients with comorbidities requiring long-term use of immunosuppressive drugs or systemic or local use of corticosteroids with immunosuppressive effects;
• Patients with active tuberculosis, or those currently receiving antituberculosis treatment or who have received antituberculosis treatment within the past year prior to screening;
• Other patients deemed ineligible for inclusion by the treating physician.

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 · 15 centers

• Anhui Provincial Cancer Hospital — Hefei
• Fujian Cancer Hospital — Fuzhou
• Sun Yat-sen University cancer center — Guangzhou
• the Affiliated Cancer Hospital of Guangzhou Medical University — Guangzhou
• Cancer Hospital of Shantou University Medical College — Shantou
• Zhongshan City People's Hospital — Zhongshan
• The Fifth Affiliated Hospital of Sun Yat-sen University — Zhuhai
• Guangxi Medical University Cancer Hospital — Nanning
• … and 7 more centers

Identifiers

NCT: NCT07328854 · ZDWY.BYAFZZX.046

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗