High-grade squamous intraepithelial lesions (HSIL), encompassing cervical intraepithelial neoplasia grade 2 (CIN2) with p16 positivity and grade 3 (CIN3), are precancerous conditions that require effective intervention. This Phase II study aims to comprehensively evaluate the efficacy, safety, and impact on quality of life of hexaminolevulinate photodynamic therapy (HAL-PDT) with deferred surgery compared to immediate surgical treatment in subjects with HSIL. This is a prospective, open-label, randomized, controlled, non-inferiority trial. A total of 230 subjects are planned to be enrolled, with 115 subjects allocated to each treatment group (HAL-PDT with Deferred Surgery or Immediate Surgery ). The primary endpoint is the pathological regression rate at 12 months, defined as histological findings of normal tissue or low-grade squamous intraepithelial lesions (LSIL) via colposcopy-directed biopsy. Key secondary endpoints include Human Papillomavirus (HPV) clearance rates at 6 and 12 months, pathological regression rate at 6 months, quality of life assessed by the EORTC QLQ-CX24 questionnaire, safety profiles (incidence, severity, and duration of AEs and SAEs, as well as their relationship to the study treatments), and the proportion of subjects developing cervical cancer within 12 months.
High-grade squamous intraepithelial lesions (HSIL), encompassing cervical intraepithelial neoplasia grade 2 (CIN2) with p16 positivity and grade 3 (CIN3), are well-established precursors to invasive cervical cancer. Immediate excisional procedures such as loop electrosurgical excision procedure (LEEP) or cold knife conization remain the standard of care; however, they are associated with significant long-term morbidities, including cervical stenosis, cervical incompetence, and adverse obstetric outcomes in women of childbearing age. Hexaminolevulinate photodynamic therapy (HAL-PDT) is a non-invasive, tissue-preserving modality that offers a potential alternative. This Phase II trial is designed to test the hypothesis that HAL-PDT (HAL-PDT Q2W×6 ) with deferred surgery achieves a 12-month pathological regression rate non-inferior to that of immediate surgery, while providing a favorable safety and quality-of-life profile. A total of 230 subjects are planned for enrollment, with 115 allocated to each treatment arm. The primary efficacy analysis will be performed on both the Intention-to-Treat (ITT) and Per-Protocol (PP) populations to test the non-inferiority margin, which is pre-specified based on clinically acceptable thresholds. Safety analyses will be conducted on the Safety Set (SS).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
230
Subjects undergo immediate surgical excision of the cervical lesion via either Loop Electrosurgical Excision Procedure (LEEP) or Cold Knife Conization (CKC), as determined by the investigator based on the subject's individual lesion characteristics, size, and clinical presentation, following standard institutional surgical protocols.
HAL-PDT is a drug-device combination product. The drug is hexaminolevulinate hydrochloride (HAL) 5% ointment. The device is a single-use cervical light delivery device (CL7) with integrated red LEDs. The ointment is applied into the device cup, placed against the cervix for 5 hours of drug absorption, then automatically delivers 125 J/cm² photodynamic therapy for 4 hours and 36 minutes. Total in-situ time is 11-24 hours. Patients remove the device themselves. Treatment regimen: one session every 2 weeks for a total of 6 sessions (Q2W × 6).
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
Xiamen Maternity and Child Healthcare Hospital
Xiamen, Fujian, China
he First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
The First People's Hospital of Foshan
Foshan, Guangdong, China
Histopathological regression rate at 12 months
Proportion of participants with pathological remission on colposcopy-directed cervical biopsy at 12 months after the first treatment. Pathological remission is defined as histopathological finding of normal tissue or low-grade squamous intraepithelial lesion (LSIL)
Time frame: 12 months after the first treatment
Human Papillomavirus (HPV) baseline clearance rate at 6 months
Proportion of participants with clearance of baseline high-risk Human Papillomavirus (HPV) subtypes at 6 months after the first treatment. HPV clearance is defined as undetectable of the same high-risk HPV subtype(s) that were present at baseline.
Time frame: 6 months after the first treatment
Pathological remission rate at 6 months
Proportion of participants with pathological remission on colposcopy-directed cervical biopsy at 6 months after the first treatment. Pathological remission is defined as histopathological finding of normal tissue or low-grade squamous intraepithelial lesion (LSIL).
Time frame: 6 months after the first treatment
HPV baseline clearance rate at 12 months
Proportion of participants with clearance of baseline high-risk HPV subtypes at 12 months after the first treatment. HPV clearance is defined as undetectable of the same high-risk HPV subtype(s) that were present at baseline.
Time frame: 12 months after the first treatment
Quality of life assessed by EORTC QLQ-CX24
Quality of life assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Cervical Cancer Module (EORTC QLQ-CX24). Scores for each domain are linearly transformed to a 0-100 scale. For global health status and functional domains, a higher score indicates a better outcome (better quality of life/function). For symptom scales, a higher score indicates a worse outcome (more severe symptoms).
Time frame: 12 months after the first treatment
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Incidence, type, severity (mild, moderate, severe), duration, and relatedness to photodynamic therapy and/or surgical treatment of adverse events (AEs) and serious adverse events (SAEs) occurring from signing of informed consent through the end of study follow-up.
Time frame: From informed consent through 12 months after the first treatment
Incidence of cervical cancer at 12 months
Proportion of participants with histologically confirmed cervical cancer (any stage) diagnosed within 12 months after the first treatment.
Time frame: 12 months after the first treatment
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Foshan Shunde Maternal and Child Health Hospital
Foshan, Guangdong, China
Guangdong Women and Children Hospital
Guangzhou, Guangdong, China
The Affiliated Cancer Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
Guangdong ProvincialHospital of Chinese Medicine
Guangzhou, Guangdong, China
Guangzhou First People's Hospital (The Second Affiliated Hospital of South China University of Technology)
Guangzhou, Guangdong, China
...and 18 more locations