Comparing two types of radiotherapy for advanced nasopharyngeal carcinoma after chemotherapy

Under Whole-course of Immunotherapy, Gradient Fractionated Radiotherapy with Concurrent Chemotherapy Versus Standard Fractionated Radiotherapy with Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma Who Achieved Partial Response After Induction Chemotherapy: a Randomized, Open-label, Multicenter, Phase III Trial.

This study is testing whether a new type of radiotherapy that lowers the dose in certain areas can help people with advanced nasopharyngeal cancer who have responded to chemotherapy feel better compared to standard treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 586 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Zhuhai, Guangdong)
• Trial ID: NCT06675214 on ClinicalTrials.gov

What this trial studies

This phase 3 trial aims to enroll patients with stage III-IVA locoregionally advanced nasopharyngeal carcinoma who have achieved a partial response after induction chemotherapy combined with PD-1/PD-L1 blockade. Participants will be randomized to receive either gradient fractionated radiotherapy, which reduces the dose in areas without metabolic abnormalities, or standard dose radiotherapy with concurrent chemotherapy. The goal is to evaluate the effectiveness of these approaches in providing a new therapeutic option for patients at moderate risk. The study focuses on improving treatment outcomes while minimizing unnecessary radiation exposure.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with histologically confirmed non-keratinizing nasopharyngeal carcinoma who have achieved a partial response after chemotherapy and immunotherapy.

Not a fit: Patients with non-advanced nasopharyngeal carcinoma or those who do not respond to initial chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a more effective and safer treatment option for patients with advanced nasopharyngeal carcinoma.

How similar studies have performed: Other studies have explored similar approaches in radiotherapy for nasopharyngeal carcinoma, indicating potential for success, though this specific method is novel.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
2. Tumor staged as III-IVA (AJCC 8th).
3. Patients who achieved partial response according to the RECIST criteria on the basis of MRI, PET-CT and endoscopic biopsy after 3 cycles of induction therapy of platinum-based chemotherapy plus immunotherapy.
4. Eastern Cooperative Oncology Group performance status ≤1.
5. Age: 18-65 years old.
6. Adequate organ function:

   Adequate marrow function: neutrocyte count≥4×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.

   Adequate liver and kidney function: Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 2.5×ULN.; creatinine clearance rate ≥ 60 ml/min or creatinine of no more than 1.5 times the upper normal limit.
7. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. Patients who are evaluated as CR or SD or PD after 3 cycles of induction therapy of platinum-based chemotherapy plus PD-1/PD-L1 blockades.
2. The laboratory examination value does not meet the relevant standards within 7 days before enrollment.
3. The images of PET-CT and enhanced MRI/CT before induction chemotherapy showed necrotic foci in the center of primary tumors or regional lymph nodes.
4. The metabolic changes shown by PET-CT images after induction chemotherapy were inconsistent with the changes in the extent of tumor invasion shown by anatomical images such as enhanced MRI/CT.
5. The primary and/or cervical metastases of patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (except diagnostic treatment).
6. Has a known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
7. Has a known or suspected history of autoimmune diseases, including dementia and seizures.
8. Patients with recurrence, distant metastasis and other malignant tumors.
9. Severe heart disease, lung dysfunction, heart function, lung function below grade 3 (including grade 3)
10. Patients who underwent anti-PD-1 /PD-L1 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway) and anti-angiogenic drugs.
11. Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
12. HIV positive; HBsAg positive and HBV DNA copy number positive (quantitative detection ≥ 1000 cps/ml); chronic hepatitis C with blood screening positive (HCV antibody positive).
13. Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
14. Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB treatment is ongoing or within 1 year prior to screening.
15. Has received a live vaccine; or a systematic glucocorticoid therapy ; or any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) ; any Chinese anti-tumor herbs within 4 weeks prior to enrollment.
16. Pregnancy or breastfeeding.
17. Other patients who were considered unsuitable by the treating physicians.

Where this trial is running

Zhuhai, Guangdong

• The Fifth Affiliated Hospital of Sun Yat-sen University — Zhuhai, Guangdong, 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; De-escalation Therapy