IC Plus Low-dose Radiation Plus Cadonilimab in LANPC

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma; Chemotherapy; Radiotherapy; Immune Checkpoint Inhibitor
• Intervention / Treatment: Radiation: Intensity Modulated Radiation Therapy; Drug: Chemotherapy; Biological: Immune checkpoint inhibitor; Radiation: Low-dose radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jingjing Miao, MD; Phone Number: +8613631355201; Email: miaojj@sysucc.org.cn
• Study Contact Backup: Name: Chong Zhao, MD, PhD; Phone Number: 02087342638; Email: zhaochong@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Cancer Center, Sun Yat-sen University
      • Contact: Chong Zhao, M.D; Phone Number: 02087342638; Email: zhaochong@sysucc.org.cn
  • Guangxi
    • Nanning, Guangxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Guangxi Medical University
      • Contact: Min Kang, MD
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • Jiangxi Cancer Hospital
      • Contact: Jingao Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose RT plus ICI; Patients will receive induction chemotherapy plus low-dose radiotherapy and immuce checkpoint inhibitor then followed by concurrent chemoradiotehrapy.	Radiation: Intensity Modulated Radiation Therapy; 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.; Other Names: IMRT; Drug: Chemotherapy; Induction chemotherapy: gemcitabine and cisplatin, Q3W, 3 cycles Concurrent chemotherapy: cisplatin, Q3W, 2-3 cycles; Other Names: Gemcitabine; Cisplatin; Concurrent chemotherapy; Induction chemotherapy; Biological: Immune checkpoint inhibitor; Cadonilimab: 10mg/kg, Q3W, 3 cycles; Other Names: AK104; Cadonilimab; PD-1/CTLA-4 inhibitor; Radiation: Low-dose radiotherapy; Low-dose radiotherapy will be performed to study group, with the use of IMRT.
Active Comparator: IC+CCRT; Patients will receive induction chemotherapy plus concurrent chemoradiotehrapy.	Radiation: Intensity Modulated Radiation Therapy; 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.; Other Names: IMRT; Drug: Chemotherapy; Induction chemotherapy: gemcitabine and cisplatin, Q3W, 3 cycles Concurrent chemotherapy: cisplatin, Q3W, 2-3 cycles; Other Names: Gemcitabine; Cisplatin; Concurrent chemotherapy; Induction chemotherapy

What is the study measuring?

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
Regional recurrence-free survival	From the date of randomization to regional recurrence or any death	3 years
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
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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Chong Zhao, MD, PhD, Sun Yat-sen University Cancer Center

Publications and helpful links

Helpful Links

• Home Page of Cancer Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: July 1, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Remission Induction; Immune Checkpoint Inhibitors; Gemcitabine; Cisplatin; Radiotherapy; Drug Therapy; Radiotherapy, Intensity-Modulated; Induction Chemotherapy
• Other Study ID Numbers: Low-dose RT in NPC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No