Under Whole-course of Immunotherapy, Gradient Fractionated RT with CCT Versus CFRT with CCT for LANPC Who Achieved PR Post Induction Chemotherapy.

Sun Yat-sen University

Status and phase: Enrolling; Phase 3

Conditions: De-escalation Therapy; Nasopharyngeal Carcinoma

Treatments: Radiation: Gradient Fractionated IMRT; Drug: Concurrent Chemotherapy; Drug: Cisplatin-based induction chemotherapy; Drug: Full course of PD-1/PD-L1 blockades; Radiation: Standard-dose IMRT

Study type: Interventional

Funder types: Other

Identifiers

NCT06675214

ZDWY.BYAFZZX.074

Details and patient eligibility

About

This prospective trial aims to enroll patients with stage III-IVA (AJCC 8th,) locoregionally advanced nasopharyngeal carcinoma (LANPC). Under the condition of full course of PD-1/PD-L1 blockades, patients who achieved radiological partial response after 3 cycles of platinum-based chemotherapy plus PD-1/PD-L1 blockades will be randomized in a 1:1 ratio to receive gradient radiotherapy (reducing the irradiation dose of PET-CT areas without metabolic abnormalities, while maintaining adequate irradiation dose of areas with metabolic abnormalities) or standard dose radiotherapy with concurrent chemotherapy. It is expected to provide a new therapeutic option for locally advanced nasopharyngeal carcinoma at moderate risk.

Enrollment: 586 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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586 participants in 2 patient groups

Induction chemotherapy plus conventional concurrent chemoradiotherapy

Active Comparator group

Treatment:

Radiation: Standard-dose IMRT

Drug: Full course of PD-1/PD-L1 blockades

Drug: Cisplatin-based induction chemotherapy

Drug: Concurrent Chemotherapy

Induction chemotherapy plus gradient fractioned radiotherapy and concurrent chemotherapy

Experimental group

Treatment:

Drug: Full course of PD-1/PD-L1 blockades

Drug: Cisplatin-based induction chemotherapy

Drug: Concurrent Chemotherapy

Radiation: Gradient Fractionated IMRT