Induction chemotherapy with low-dose radiation and cadonilimab for locally advanced nasopharyngeal carcinoma

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 study will try adding low-dose radiation and the immune drug cadonilimab to induction chemotherapy before standard concurrent chemoradiotherapy in adults with newly diagnosed locally advanced nasopharyngeal carcinoma.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 380 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 3 sites (Guangzhou, Guangdong and 2 other locations)
• Trial ID: NCT05941741 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized phase III trial comparing induction chemotherapy combined with low-dose radiation and cadonilimab followed by concurrent chemoradiotherapy versus induction chemotherapy followed by standard concurrent chemoradiotherapy. Eligible patients are adults 18–70 years with newly diagnosed non-keratinizing loco-regionally advanced nasopharyngeal carcinoma (T4N1M0 or T1-4N2-3M0) and ECOG 0–1. Interventions include intensity-modulated radiation therapy, standard chemotherapy, low-dose radiotherapy during induction, and the immune checkpoint inhibitor cadonilimab, with participants randomized to the experimental or control arm. Primary outcomes compare treatment efficacy, treatment-related adverse events, and patient-reported quality of life between the two groups with planned follow-up for survival and toxicity.

Who should consider this trial

Good fit: Ideal candidates are adults 18–70 with newly diagnosed, non-keratinizing (WHO II/III) loco-regionally advanced nasopharyngeal carcinoma (specified T/N stages), ECOG 0–1, adequate organ function, and no prior anti-cancer therapy.

Not a fit: Patients with distant metastases, keratinizing histology or other active malignancies, poor organ function, contraindications to chemo/radiation/immunotherapy, or ECOG performance status >1 are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could improve local control and survival while maintaining acceptable toxicity and quality of life for patients with locally advanced nasopharyngeal carcinoma.

How similar studies have performed: Previous phase II/III studies adding PD-1 immune checkpoint inhibitors to chemotherapy and radiotherapy in nasopharyngeal carcinoma have shown improved outcomes, but combining low-dose radiation with cadonilimab is a newer strategy with limited prior data.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong and 2 other locations

• Cancer Center, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (Not_yet_recruiting)
• Jiangxi Cancer Hospital — Nanchang, Jiangxi, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Chong Zhao, MD, PhD — Sun Yat-Sen University Cancer Center
• Study coordinator: Chong Zhao, MD, PhD

Conditions Nasopharyngeal Carcinoma; Immune Checkpoint Inhibitor; Radiotherapy; Chemotherapy