Compare Radiotherapy Plus Nimotuzumab Versus Radiotherapy Alone in Platinum-ineligible Patients With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

An Open-label, Prospective, Randomized, Phase III, International Multicenter Clinical Study to Compare Radiotherapy Plus Nimotuzumab Versus Radiotherapy Alone in Platinum-Ineligible Patients With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC)

This is an open-label, prospective, randomized, Phase III, international multicenter clinical study to compare radiotherapy plus nimotuzumab versus radiotherapy alone in platinum-ineligible patients with locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC),

Study Overview

• Status: Recruiting
• Conditions: Head & Neck Cancer; Head & Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Nimotuzumab; Radiation: intensity-modulated technique（IMRT）

Detailed Description

This is an open-label, prospective, randomized, Phase III, international multicenter clinical study to compare radiotherapy plus nimotuzumab versus radiotherapy alone in platinum-ineligible patients with locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC), The study aims to evaluate the efficacy and safety of radiotherapy combined with nimotuzumab in platinum-ineligible patients with (LA-HNSCC).Around 70 study sites were involved in the trial.

• Study Type: Interventional
• Enrollment (Estimated): 335
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Man Hu; Phone Number: （0531）67626151 86+15806698606; Email: hu5770@sina.com

Study Locations

• China
  • Province
    • Shandong, Province, China
      • Recruiting
      • Shandong First Medical University Affiliated Cancer Hospital
      • Contact: Man Hu; Phone Number: （0531）67626151 86+15806698606; Email: hu5770@sina.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eligible subjects must meet all of the following:

  • Age ≥18 years.
  • Histologically confirmed stage III-IVB (AJCC 8th edition) head and neck squamous cell carcinoma (including cancers of the oral cavity, oropharynx, hypopharynx, and larynx).
  • Unsuitable for surgical treatment (defined as: due to patient condition or tumor factors [T3-4 N0-3 M0, or T1-2 N2-3 M0] or medical reasons, surgery is not feasible; or an R0 resection is not achievable).
  • Suitable for definitive radiotherapy with curative intent.
  • At least one of the following reasons for being unsuitable for cisplatin-based chemotherapy:
• Age ≥65 years and, in the investigator's judgment, unable to tolerate chemotherapy;
• ECOG Performance Status >2 (if this criterion is met, the ECOG criterion listed below may be waived);
• Renal dysfunction: creatinine clearance (CrCl) <50 mL/min (Cockcroft-Gault) (if this criterion is met, the renal function criterion listed below may be waived);
• Severe tinnitus or hearing loss (requires a hearing aid or audiometry shows ≥25 dB loss at two consecutive frequencies);
• Peripheral neuropathy > Grade 1;

• Inability to receive intravenous hydration (e.g., due to cardiac dysfunction) or other comorbidities, per investigator's judgment.

  • Provide tumor tissue, whenever possible, for EGFR testing; for oropharyngeal cancer, provide tissue for HPV/p16 testing if feasible (no need to retest if previously tested).
  • ECOG Performance Status 0-1 (or Karnofsky Performance Status ≥80).
  • At least one measurable lesion per RECIST 1.1.
  • Expected survival ≥6 months.
  • Adequate hematologic function: WBC ≥4×10^9/L; absolute neutrophil count ≥1.5×10^9/L; platelets ≥100×10^9/L; hemoglobin ≥90 g/L.
  • Adequate renal function: serum creatinine ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault):
• Female CrCl = (140 - age) × weight (kg) × 0.85 / (72 × S_cr [mg/dL])

• Male CrCl = (140 - age) × weight (kg) × 1.00 / (72 × S_cr [mg/dL])

  • Adequate liver function: total bilirubin ≤1.5×ULN; AST ≤2.5×ULN; ALT ≤2.5×ULN.
  • Voluntary participation: signed written informed consent and ability to comply with visits and procedures.

Exclusion Criteria:

• Any of the following excludes enrollment:

  • Receipt of a PD-1 inhibitor, EGFR monoclonal antibody, EGFR-TKI, or anti-angiogenic agent within 4 weeks prior to enrollment.
  • Participation in another interventional clinical trial within 30 days prior to screening.
  • History of other malignancy (except cured basal cell carcinoma of the skin).
  • History of primary immunodeficiency.
  • Uncontrolled comorbid conditions (e.g., congestive heart failure, severe pulmonary disease, severe liver disease, psychiatric illness).
  • Known HIV infection, or active viral hepatitis or active tuberculosis.
  • Major surgery within 90 days before first study treatment, or planned surgery during the study.
  • Known allergy to nimotuzumab or its excipients.
  • Deemed unsuitable to participate by the investigator.
  • Unwilling or unable to sign informed consent.
  • Receipt of a live vaccine within 30 days before first dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy plus nimotuzumab; radiotherapy plus nimotuzumab	Drug: Nimotuzumab; Treatment regimen： Nimotuzumab(Experimental Group): nimotuzumab injection 200 mg IV once weekly (QW) for 7 weeks (concurrent with radiotherapy).; Other Names: Nimotuzumab injection; Radiation: intensity-modulated technique（IMRT）; Treatment regimen： Radiotherapy (both groups): intensity-modulated technique (photon IMRT or proton IMPT); total dose 70 Gy (2.0 Gy per fraction, 35 fractions), 5 fractions per week.; Other Names: photon IMRT; proton IMPT; intensity-modulated technique
Active Comparator: Radiotherapy alone in LA-HNSCC	Radiation: intensity-modulated technique（IMRT）; Treatment regimen： Radiotherapy (both groups): intensity-modulated technique (photon IMRT or proton IMPT); total dose 70 Gy (2.0 Gy per fraction, 35 fractions), 5 fractions per week.; Other Names: photon IMRT; proton IMPT; intensity-modulated technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	the proportion of patients in a clinical study who remain free of disease progression (including local recurrence, regional lymph node metastasis, distant metastasis, or second primary malignancy) and have not died from any cause within 2 years from the start of treatment (or randomization in randomized controlled trials).	24 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year locoregional control (LRC) rate.	the proportion of patients in a clinical study who remain free of disease progression within 2 years from the start of treatment (or randomization in randomized controlled trials).	24 months after treatment initiation
2-year distant metastasis rate.	the prproportion of participants with distant metastatic progression within 24 months,	24 months after treatment initiation
Overall Survival (OS)	the prproportion of participants surviving at 2 years after enrolling,regardless of disease status.	24 months after treatment initiation
Objective Response Rate (ORR; CR+PR by RECIST 1.1).	the proportion of patients with measurable malignant tumors who achieve a complete response (CR) or partial response (PR)	24 months after treatment initiation
Quality of Life (QoL)		24 months after treatment initiation

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: Man Hu, Shandong First Medical University Affiliated Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 5, 2026
• Primary Completion (Estimated): January 5, 2028
• Study Completion (Estimated): January 5, 2030

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: December 30, 2025
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Radiotherapy; Nimotuzumab; LA-HNSCC; locoregionally advanced head and neck squamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; nimotuzumab
• Other Study ID Numbers: IST-Nim-HNSCC-45

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