Re-irradiation with chidamide for recurrent head and neck squamous cell carcinoma

A Prospective, Single-arm Clinical Study on Re-irradiation Combined With Chidamide in the Treatment of Patients With Recurrent Head and Neck Squamous Cell Carcinoma After Radiotherapy

This trial will test whether adding the drug chidamide to repeat radiation is safe and tolerable for adults whose head and neck squamous cell carcinoma has returned after prior radiotherapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07545967 on ClinicalTrials.gov

What this trial studies

This phase 1, single-center dose-escalation trial at West China Hospital combines oral chidamide with salvage intensity-modulated re-irradiation for adults with recurrent HNSCC. Participants receive IMRT 60 Gy in 30 fractions over six weeks alongside chidamide given twice weekly at 20 mg or 30 mg using a 3+3 dose-escalation design with at least three days between doses. The primary focus is safety, including determining dose-limiting toxicities and tolerability, with adverse events graded per CTCAE v5.0 and routine labs and clinical evaluations throughout treatment. Patients will undergo safety follow-up and longer-term monitoring for tumor response and survival outcomes according to the protocol.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed recurrent squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx who previously received radiotherapy at least six months earlier, have unresectable disease or decline surgery, an ECOG 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients who are surgical candidates, have poor performance status, inadequate organ or marrow function, recent prior radiotherapy within six months, or widespread metastatic disease are unlikely to benefit from this re-irradiation approach.

Why it matters

Potential benefit: If safe and tolerable, the combination could provide a new salvage option that may improve local control for patients with recurrent, unresectable head and neck cancer.

How similar studies have performed: Preclinical studies and limited early-phase clinical work suggest HDAC inhibitors can sensitize tumors to radiation, but combining chidamide with re-irradiation in recurrent HNSCC is relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

1. Age and Life Expectancy: Aged ≥18 and ≤75 years, with a life expectancy of ≥3 months, regardless of gender.
2. Diagnosis and History: Patients with histologically confirmed head and neck squamous cell carcinoma meeting the following conditions:

   1. Primary tumor site located in the oral cavity, oropharynx, larynx, or hypopharynx.
   2. History of prior radical or adjuvant radiotherapy with local/regional recurrence (confirmed by MRI/PET-CT).
   3. The interval between the completion of the last radiotherapy and recurrence is ≥6 months (to ensure partial recovery of normal tissues).
3. Surgical Status: The recurrent lesion is deemed unresectable by a head and neck surgeon, or the patient refuses surgery, or is medically unfit to tolerate surgery.
4. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
5. Organ and Marrow Function: Adequate organ and bone marrow function, defined as follows:

   1. Hematology: Absolute Neutrophil Count (ANC) ≥1.5×10⁹/L; Platelets (PLT) ≥80×10⁹/L; Hemoglobin ≥8 g/dL.
   2. Liver Function: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline Phosphatase (ALP) ≤2.5× Upper Limit of Normal (ULN); Total Bilirubin (TBIL) ≤1.5×ULN.
   3. Albumin: Serum Albumin ≥2.8 g/dL.
   4. Renal Function: Serum Creatinine (Cr) ≤1.5×ULN OR Creatinine Clearance (CrCl) \>60 mL/min.
   5. Coagulation: International Normalized Ratio (INR) ≤1.5; Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN.
6. Consent: Willingness to participate in the study, evidenced by signing the Informed Consent Form (ICF), and ability to comply with scheduled visits and related procedures.

Exclusion Criteria:

1. Metastatic Disease: Presence of distant metastasis (Stage M1).
2. Prior Therapy: Receipt of any of the following treatments:

   1. Prior treatment with HDAC inhibitors (e.g., chidamide, vorinostat), etc.
   2. Major surgery or severe trauma within 4 weeks prior to the first dose.
3. Second Primary Malignancy: History of a second primary malignancy (excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or carcinoma of the gastrointestinal tract in situ that has been cured with no recurrence for 5 years, or other malignancies deemed eligible by the Investigator).
4. Prior Toxicity: Occurrence of Grade ≥3 radiation necrosis or myelosuppression following the initial radiotherapy.
5. Medical Comorbidities: Presence of severe medical illnesses, such as:

   1. Cardiac insufficiency Class II or higher (NYHA criteria);
   2. Ischemic heart disease (e.g., myocardial infarction or angina pectoris);
   3. Clinically significant supraventricular or ventricular arrhythmias;
   4. Left Ventricular Ejection Fraction (LVEF) \<50% as determined by echocardiogram;
   5. QTc interval \>450 msec for males or \>470 msec for females;
   6. Abnormal Electrocardiogram(ECG) findings that the Investigator considers to pose an additional risk for the investigational drug.
6. Infectious Disease: Presence of active Hepatitis B (Hepatitis B Virus Deoxyribonucleic Acid ≥2000 IU/ml or 10⁴ copies/ml) or Hepatitis C (Hepatitis C Virus antibody positive and Hepatitis C Virus Ribonucleic Acid above the lower limit of detection of the assay), or a known history of positive Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS).
7. Psychiatric Disorders: Any severe neurological or psychiatric illness that may prevent the patient from providing informed consent or complying with study procedures.
8. Reproductive Status: Women who are pregnant or breastfeeding; subjects (and their partners) who plan to conceive during the screening period up to 3 months after the end of the study; or women of childbearing potential who are not using effective contraceptive methods.
9. Investigational Drugs: Receipt of any investigational drug within 4 weeks prior to the first dose of the study drug, or concurrent enrollment in another clinical study, unless it is for observational or interventional clinical study follow-up.
10. Investigator Discretion: Other factors determined by the Investigator that may affect the subject's ability to complete the study medication and follow-up.

Where this trial is running

Chengdu, Sichuan

• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Xingchen Peng — West China Hospital
• Study coordinator: Xingchen Peng

Conditions Head and Neck Squamous Cell Carcinoma HNSCC