Pirfenidone as a Radiosensitizer in the Treatment of Head and Neck Squamous Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with a 5-year survival rate of less than 50%. Radiotherapy is an important measure to control tumor recurrence. Although radiotherapy has been widely used in patients with head and neck squamous cell carcinoma, the 2-year local recurrence rate of patients with locally advanced disease is still as high as 50%-60%, and the distant metastasis rate is as high as 20%-30%. This is associated with a lower radiosensitivity in HNSCC. Our previous study has confirmed that type I collagen secreted by cancer-associated fibroblasts (CAFs) can enhance the radioresistance of head and neck squamous cell carcinoma. We also confirmed that pirfenidone could reduce type I collagen expression in CAFs and enhance radiosensitivity in vitro and in vivo. Therefore, we plan to translate the basic research into clinical practice and conduct a prospective interventional phase II clinical trial to investigate the safety and efficacy of pirfenidone as a radiosensitizer in HNSCC.

Official Title
-----------------
Application of Pirfenidone as a Radiosensitizer in the Treatment of Head and Neck Squamous Cell Carcinoma: Phase II Clinical Study

Conditions
-----------------
Head and Neck Squamous Cell Carcinoma, Radiotherapy, Radiosensitizer, Pirfenidone

Intervention / Treatment
-----------------
* Drug: Pirfenidone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: be at least 18 years old; provide written informed consent; head and neck squamous cell carcinoma confirmed by biopsy (2022 WHO criteria); no previous head and neck radiotherapy; The presence of measurable lesions: no surgical treatment or postoperative imaging evaluation indicated that the tumor was not completely resected; ECOG PS: 0/1; Laboratory confirmation of good organ function. It should be given within 10 days before the first dose of treatment; 8) expected survival time ≥3 months. Exclusion Criteria: no indications for or contraindications to radiotherapy after evaluation; no oral medication; pregnancy or lactation; patients with known allergy to pirfenidone or other contraindications; concurrent tumors (except cured basal cell or squamous cell skin cancer, and cervical cancer in situ); patients had any serious coexisting medical conditions that could pose an unacceptable risk or negatively affect trial adherence. For example, unstable heart disease requiring treatment, chronic hepatitis, kidney disease, poor condition, uncontrolled diabetes (fasting blood glucose > 1.5 × ULN), and mental illness.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pirfenidone group<br>Calculate from 2 weeks before the start of radiotherapy: week 1: pirfenidone 200mg, tid; week 2: pirfenidone 400mg tid; during radiotherapy: pirfenidone 600mg tid. | Drug: Pirfenidone<br>* Dose climbing started two weeks before the start of radiotherapy, and the maintenance dose of 600mg bid was reached in the third week until the end of radiotherapy.<br>|
| Placebo Comparator: Control group<br>Calculate from 2 weeks before the start of radiotherapy: week 1: placebo 200mg, tid; week 2: placebo 400mg tid; during radiotherapy: placebo 600mg tid. | Drug: Placebo<br>* Dose climbing started two weeks before the start of radiotherapy, and the maintenance dose of 600mg bid was reached in the third week until the end of radiotherapy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The objective response rate (ORR) is the proportion of patients who achieve a prespecified reduction in tumor volume that is maintained for a minimum duration. The objective response rate was defined as the sum of complete response plus partial response (CR+PR). According to RECIST1.1 criteria, CR was defined as the disappearance of target lesions and the reduction of the short diameter of pathological lymph nodes to less than 10mm. PR: the sum of the measured diameters of the target lesions reduced by 30% compared with the baseline; PD: the sum of the major diameters of all target lesions increased by at least 20%, and the absolute value of the sum of the major diameters increased by more than 5mm, or new lesions appeared. SD: Changes between PR and PD. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS was defined as the time from the date of inclusion until death from any cause. | 2 years | 
| Incidence of Treatment-Emergent Adverse Events | treatment-related adverse events will be assessed by CTCAE v5.0 | During treatment and 12 weeks after treatment |