Lower-dose (40.2 Gy) versus standard-dose (49.2 Gy) radiotherapy to low‑risk areas for chemosensitive Stage II nasopharyngeal cancer

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

This trial will try a lower radiotherapy dose (40.2 Gy) instead of the standard 49.2 Gy for people with stage II nasopharyngeal cancer who had a strong response to induction chemo and have undetectable EBV DNA.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 346 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 15 sites (Hefei, Anhui and 14 other locations)
• Trial ID: NCT07328854 on ClinicalTrials.gov

What this trial studies

This randomized phase 3 trial enrolls low‑risk, chemosensitive Stage II nasopharyngeal carcinoma patients who achieve a complete or partial response and undetectable plasma EBV DNA after induction cisplatin‑based chemotherapy plus PD‑1 immunotherapy. Eligible patients are randomized 1:1 to receive either reduced‑dose radiotherapy (40.2 Gy) or conventional‑dose radiotherapy (49.2 Gy) to the low‑risk clinical target volume (CTV2), with both arms receiving a full course of immunotherapy. Investigators will follow participants for survival outcomes, acute and late adverse events, and health‑related quality of life. The trial tests whether lowering the dose to CTV2 can preserve cancer control while reducing treatment‑related toxicity and improving quality of life.

Who should consider this trial

Good fit: Adults 18–75 with non‑keratinizing Stage II (T1‑3N2M0 or T3N0‑1M0) nasopharyngeal carcinoma who achieved CR or PR after three cycles of cisplatin‑based induction chemo plus PD‑1 therapy, have EBV DNA reduced to undetectable, KPS ≥70, and adequate organ function are ideal candidates.

Not a fit: Patients with recurrent or metastatic disease, those who do not achieve a strong response to induction therapy or who still have detectable EBV DNA, or those with poor organ function or performance status are unlikely to benefit from this dose‑reduction approach.

Why it matters

Potential benefit: If successful, patients could maintain tumor control while experiencing fewer acute and chronic radiation toxicities, leading to better quality of life.

How similar studies have performed: Early-phase trials and retrospective series in nasopharyngeal and other head‑and‑neck cancers suggest dose de‑escalation after excellent treatment response can reduce toxicity without compromising control, but definitive phase‑III evidence in nasopharyngeal carcinoma remains limited.

Eligibility criteria

Inclusion Criteria:

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

1. Patients with recurrent/metastatic nasopharyngeal carcinoma;
2. Pregnant or breastfeeding women (pregnancy tests should be considered for women of childbearing age; effective contraception should be emphasised during treatment);
3. 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;
4. 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;
5. 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;
6. Patients with a history of severe hypersensitivity reactions to any component of PD-1 monoclonal antibodies;
7. History of allergic reactions to the chemotherapy drugs used in this study (gemcitabine, docetaxel, albumin-bound paclitaxel, paclitaxel, cisplatin);
8. Patients with comorbidities requiring long-term use of immunosuppressive drugs or systemic or local use of corticosteroids with immunosuppressive effects;
9. Patients with active tuberculosis, or those currently receiving antituberculosis treatment or who have received antituberculosis treatment within the past year prior to screening;
10. Other patients deemed ineligible for inclusion by the treating physician.

Where this trial is running

Hefei, Anhui and 14 other locations

• Anhui Provincial Cancer Hospital — Hefei, Anhui, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Sun Yat-sen University cancer center — Guangzhou, Guangdong, China (Recruiting)
• the Affiliated Cancer Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (Recruiting)
• Cancer Hospital of Shantou University Medical College — Shantou, Guangdong, China (Recruiting)
• Zhongshan City People's Hospital — Zhongshan, Guangdong, China (Recruiting)
• The Fifth Affiliated Hospital of Sun Yat-sen University — Zhuhai, Guangdong, China (Recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Recruiting)
• Wuzhou Red Cross Hospital — Wuzhou, Guangxi, China (Recruiting)
• Central South University Cancer Hospital, — Changsha, Hunan, China (Recruiting)
• Xiangya Hospital of Central South University — Changsha, Hunan, China (Recruiting)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)
• The First Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (Recruiting)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Ming-Yuan Chen, MD,PhD — Sun Yat-sen University
• Study coordinator: Ming-Yuan Chen, MD,PhD

Conditions Nasopharyngeal Carcinoma; Reduced-dose radiotherapy; Complete response; Partial response; Epstein-Barr Virus DNA; Low-risk target volume