IC Plus Low-dose Radiation Plus Cadonilimab in LANPC

Study Overview
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Brief Summary
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This is a multi-center, open-label, randomized controlled phase III clinical trial in primary diagnosed loco-regionally advanced nasopharyngeal carcinoma (NPC) patients. The purpose of this study is to evaluate the efficacy of induction chemotherapy (IC) combined with low-dose radiation and immune checkpoint inhibitor (ICI) followed by concurrent chemoradiotherapy (CCRT) versus IC+CCRT, and compare the treatment-related adverse events and quality of life in two groups.

Official Title
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Induction Chemotherapy Combined With Low-dose Radiation Plus Cadonilimab in Loco-regionally Advanced Nasopharyngeal Carcinoma: a Multi-center, Open-label, Randomized Controlled Phase III Clinical Trial

Conditions
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Nasopharyngeal Carcinoma, Immune Checkpoint Inhibitor, Radiotherapy, Chemotherapy

Intervention / Treatment
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* Radiation: Intensity Modulated Radiation Therapy
* Drug: Chemotherapy
* Biological: Immune checkpoint inhibitor
* Radiation: Low-dose radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly histologic diagnosis of nasopharyngeal non-keratinizing carcinoma (WHO II/III); All genders, range from 18-70 years old; ECOG score 0-1; Clinical stage T4N1M0 and T1-4N2-3M0 (AJCC/UICC 8th); Not received radiotherapy, chemotherapy and other anti-tumor treatment (including immunotherapy); No contraindications to chemotherapy, radiotherapy or immunotherapy; Adequate organ function: white blood cell count ≥ 4×109/L, neutrophile granulocyte count ≥ 1.5×109/L, hemoglobin ≥ 9g/L, platelet count ≥ 100×109/L; alanine aminotransferase or aspartate aminotransferase < 2.5×upper limit of normal; blood urea nitrogen or creatinine ≤ 1.5×upper limit of normal or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula); Sign the consent form. Exclusion Criteria: Distant metastases; Keratinized squamous cell carcinoma or basal cell like squamous cell carcinoma; Have or are suffering from other malignant tumors; Participating in other clinical trials; Pregnancy or lactation; Have uncontrolled cardiovascular disease; Severe complication, eg, uncontrolled hypertension; Mental disorder; Drug or alcohol addition; Do not have full capacity for civil acts.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose RT plus ICI<br>Patients will receive induction chemotherapy plus low-dose radiotherapy and immuce checkpoint inhibitor then followed by concurrent chemoradiotehrapy. | Radiation: Intensity Modulated Radiation Therapy<br>* All target volumes will be outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes are defined in accordance with the International Commission on Radiation Units and Measurements Reports 83. The prescribed dose is 70-72 Gy to PTVp (Planning target volume of the primary tumor), 64-70 Gy to PTVn (Planning target volume of the lymph node), 60- 64Gy to PTV1 (High-risk planning target volume), and 54-58 Gy to PTV2 (Low-risk planning target volume) in 30-32 fractions.<br>* Other names: IMRT;Drug: Chemotherapy<br>* Induction chemotherapy: gemcitabine and cisplatin, Q3W, 3 cycles Concurrent chemotherapy: cisplatin, Q3W, 2-3 cycles<br>* Other names: Cisplatin;Biological: Immune checkpoint inhibitor<br>* Cadonilimab: 10mg/kg, Q3W, 3 cycles<br>* Other names: PD-1/CTLA-4 inhibitor;Radiation: Low-dose radiotherapy<br>* Low-dose radiotherapy will be performed to study group, with the use of IMRT.<br>|
| Active Comparator: IC+CCRT<br>Patients will receive induction chemotherapy plus concurrent chemoradiotehrapy. | Radiation: Intensity Modulated Radiation Therapy<br>* All target volumes will be outlined slice by slice on the axial contrast-enhanced CT with MR fusion images in the treatment planning system. The target volumes are defined in accordance with the International Commission on Radiation Units and Measurements Reports 83. The prescribed dose is 70-72 Gy to PTVp (Planning target volume of the primary tumor), 64-70 Gy to PTVn (Planning target volume of the lymph node), 60- 64Gy to PTV1 (High-risk planning target volume), and 54-58 Gy to PTV2 (Low-risk planning target volume) in 30-32 fractions.<br>* Other names: IMRT;Drug: Chemotherapy<br>* Induction chemotherapy: gemcitabine and cisplatin, Q3W, 3 cycles Concurrent chemotherapy: cisplatin, Q3W, 2-3 cycles<br>* Other names: Cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | From the date of randomization to local or regional recurrence, distant metastasis or any death | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the date of randomization to any death, with patients unavailable for follow-up censored at the date of last follow-up | 3 years | 
| Local recurrence-free survival | From the date of randomization to local recurrence or any death | 3 years | 
| Regional recurrence-free survival | From the date of randomization to regional recurrence or any death | 3 years | 
| Distant metastasis-free survival | From the date of randomization to distant metastasis or any death | 3 years | 
| Acute toxicities | Assessed with CTCAE v5.0 | From the start of treatment until 3 months post treatment | 
| Late toxicities | Assessed with RTOG/EORTC | 3 years post treatment | 
| Quality of life score | Assessed with EORTC-Quality of life questionnaire-C30 version 3.0 | Through study completion, an average of 3 years |