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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma; Radiotherapy; Pirfenidone; Radiosensitizer
• Intervention / Treatment: Drug: Pirfenidone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fuzhou, China
    • Not yet recruiting
    • Fujian Provinical Hospital
    • Contact: Yongmei Dai
  • Huizhou, China
    • Not yet recruiting
    • Huizhou Central People's Hospital
    • Contact: Yunming Tian
  • Jieyang, China
    • Not yet recruiting
    • Jieyang People's Hospital
    • Contact: Peibao Lai
  • Meizhou, China
    • Not yet recruiting
    • Meizhou People's Hospital, Meizhou Academy of Medical Sciences Meizhou
    • Contact: Jianda Sun
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Southern Medical University
      • Contact: Jian Guan, M.D.; Phone Number: 86+13632102247; Email: guanjian5461@163.com
      • Principal Investigator: Jian Guan, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. be at least 18 years old;
2. provide written informed consent;
3. head and neck squamous cell carcinoma confirmed by biopsy (2022 WHO criteria);
4. no previous head and neck radiotherapy;
5. The presence of measurable lesions: no surgical treatment or postoperative imaging evaluation indicated that the tumor was not completely resected;
6. ECOG PS: 0/1;
7. 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:

1. no indications for or contraindications to radiotherapy after evaluation;
2. no oral medication;
3. pregnancy or lactation;
4. patients with known allergy to pirfenidone or other contraindications;
5. concurrent tumors (except cured basal cell or squamous cell skin cancer, and cervical cancer in situ);
6. 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."

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pirfenidone group; 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; 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.
Placebo Comparator: Control group; 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; 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.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
the biomarkers correlated with ORR and OS	The correlations between ORR, OS and cancer associated fibroblasts, collagen type I, PD-L1 expression in tissues, tumor mutation burden, tumor-related gene changes, plasma cytokines or other biomarkers were explored.	2 years

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): January 30, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 21, 2023

Study Record Updates

• Last Update Posted (Actual): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: NFEC-2023-477

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