Head and Neck Squamous Cell Carcinoma, Radiation-Induced Skin Fibrosis
Conditions
Brief summary
This phase I, open-label, single-arm, non-randomized clinical trial uses a "3+3" dose-escalation design to evaluate the safety, tolerability, and preliminary efficacy of intradermal delivery of complement factor H (CFH) fragment (human, 860-1231aa) via ice microneedles for the prevention of radiation-induced skin fibrosis in patients with head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) receiving postoperative adjuvant radiotherapy. The main questions are: 1. The safety profile, including dose-limiting toxicities (DLTs) within 28 days after the first dose, adverse events, and tolerability. 2.Preliminary efficacy, assessed by changes in irradiated skin thickness, palpation of fibrotic area, CTCAE grade ≤2 fibrosis rate, and quality of life. Participants receive CFH ice microneedle patches twice weekly for a total of 8 doses (starting at 0.5 mg, escalating to 1.0 mg and 2.0 mg), applied to the skin area to be irradiated.
Interventions
BIOLOGICALCFH Protein-loaded Ice Microneedles (0.5 mg)
Recombinant human CFH protein delivered intradermally via ice microneedle patches at a total dose of 0.5 mg per administration, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.
BIOLOGICALCFH Protein-loaded Ice Microneedles (1.0 mg)
Recombinant human CFH protein delivered intradermally via ice microneedle patches at a total dose of 1.0 mg per administration, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.
BIOLOGICALCFH Protein-loaded Ice Microneedles (2.0 mg)
Recombinant human CFH protein delivered intradermally via ice microneedle patches at a total dose of 2.0 mg per administration, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 18 to 75 years (inclusive) at screening. 2. Histologically confirmed head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) scheduled to receive postoperative adjuvant radiotherapy. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 4. Adequate major organ function within 7 days before treatment, meeting the following criteria: Hemoglobin ≥ 80 g/L; neutrophil count \> 1.5 × 10⁹/L; platelet count ≥ 80 × 10⁹/L; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT or AST ≤ 2.5 × ULN (or ≤ 5 × ULN in the presence of liver metastases); Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula); Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN (unless on warfarin anticoagulation); Left ventricular ejection fraction (LVEF) ≥ 50%. 5. Ability to understand and voluntarily sign a written informed consent form prior to any study procedures.
Exclusion criteria
1. Presence of ulceration or open wound in the treatment area, or any contraindication to cutaneous administration including: Inflammation, trauma, or skin breakdown at the administration site; Severe bleeding or coagulation tendency (e.g., markedly low platelet or clotting factors); Any abnormality or permanent body art (e.g., tattoo) at the administration site that would interfere with observation of local reactions; 2. Presence of connective tissue disease or other systemic dermatologic conditions (e.g., systemic lupus erythematosus, dermatomyositis, polymyositis, systemic sclerosis, scleroderma, toxic epidermal necrolysis, Stevens-Johnson syndrome, etc.). 3. Known allergy to the investigational drug (including any excipients) or history of severe allergic reactions to any drug, food, or vaccine, such as anaphylactic shock, laryngeal edema, anaphylactic dyspnea, Henoch-Schönlein purpura, thrombocytopenic purpura, or Arthus reaction. 4. Any uncontrolled clinical disease (e.g., respiratory, circulatory, digestive, nervous, hematologic, genitourinary, or endocrine system disease) or psychiatric disorder (e.g., depression, schizophrenia) that, in the investigator's judgment, would interfere with providing informed consent, interpretation of study results, pose additional risk to the patient, or otherwise compromise study objectives. 5. Participation in another clinical trial of a drug or device within 3 months prior to screening. 6. History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism or drug addiction). 7. Pregnant or breastfeeding women, or women/partners planning pregnancy during the period from screening through 12 months after the last dose. 8. Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | First 28 days after the first study drug administration | Number of participants experiencing DLT within 28 days after the first dose of CFH protein delivered via ice microneedles. |
| Incidence and Severity of Adverse Events (AEs) | Total study period up to approximately 6 months post-radiotherapy | Number of participants with adverse events, graded according to NCI CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Irradiated Skin Thickness | Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy | Change in skin thickness of the irradiated area measured by ultrasound. |
| Change in Palpable Fibrotic Area (Surface Area and Volume) | Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy | Change in surface area (length × width) and volume (surface area × thickness) of palpable skin fibrosis in the irradiated area. |
| Number of Participants with CTCAE Grade ≤2 Fibrosis | Within 6 months after completion of radiotherapy | Number of participants who develop radiation-induced skin fibrosis of grade ≤2 according to NCI CTCAE v5.0. |
| Change in Skindex Life Quality Index (SQLI) score-16 | Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy | Change in QoL scores assessed by SQLI-16 questionnaires. Minimum Value：0 Maximum Value：100 Higher Score Means：Worse outcome (higher score indicates greater impairment of quality of life) |
| Change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score | Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy | Change in QoL scores assessed by QLQ-C30 questionnaires. Minimum Value：0 Maximum Value：100 Higher Score Means：For Global Health Status / QoL scale：Better outcome |
| Change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module (EORTC QLQ-H&N35) score | Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy | Change in QoL scores assessed by QLQ-H\&N35 questionnaires. Minimum Value：0 Maximum Value：100 Higher Score Means：Worse outcome (higher score indicates more severe symptoms/problems) |
| Change in Dermatology Life Quality Index (DLQI) score | Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy | Change in QoL scores assessed by DLQl questionnaires. Minimum Value：0 Maximum Value：30 Higher Score Means：Worse outcome (higher score indicates greater impairment of skin-related quality of life) |
Countries
China
Contacts
CONTACTXingchen Peng, MD, PhD
Outcome results
None listed