Under Whole-course of Immunotherapy, Gradient Fractionated RT with CCT Versus CFRT with CCT for LANPC Who Achieved PR Post Induction 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.
Sun Yat-sen University
586 participants
Jul 30, 2024
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria9
- Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
- Tumor staged as III-IVA (AJCC 8th).
- 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.
- Eastern Cooperative Oncology Group performance status ≤1.
- Age: 18-65 years old.
- 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.
- Patients must be informed of the investigational nature of this study and give written informed consent.
Exclusion Criteria17
- 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.
- The laboratory examination value does not meet the relevant standards within 7 days before enrollment.
- 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.
- 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.
- The primary and/or cervical metastases of patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (except diagnostic treatment).
- Has a known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
- Has a known or suspected history of autoimmune diseases, including dementia and seizures.
- Patients with recurrence, distant metastasis and other malignant tumors.
- Severe heart disease, lung dysfunction, heart function, lung function below grade 3 (including grade 3)
- 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.
- Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
- 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).
- Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
- Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB treatment is ongoing or within 1 year prior to screening.
- 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.
- Pregnancy or breastfeeding.
- Other patients who were considered unsuitable by the treating physicians.
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Interventions
a) Camrelizumab 200mg, b) Toripalimab 240mg, or c) Adebrelimab 1200mg will be started on day 1 of induction chemotherapy and given every 3 weeks for up to 12 cycles, or until intolerable toxicity, or disease progression or withdrawal from the treatment.
Cisplatin-based induction chemotherapy will be given every 3 weeks for 3 cycles before radiotherapy.
GTVnx/nd:69.96Gy/33Fr/2.12Gy CTV1: 60.60Gy/33Fr/1.82y CTV2: 54.12Gy/33Fr/1.64Gy
GTVresidue: 68Gy/30Fr/2.27Gy GTVmcr: 60Gy/30F/2Gy CTV1:54Gy/30F/1.8Gy CTV2: 48GY/30F/1.60Gy
Cisplatin 100mg/m2 every 3 weeks for 2 cycles
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06675214