Hexaminolevulinate Photodynamic Therapy (HAL-PDT) With Deferred Surgery Versus Surgery for High-grade Squamous Intraepithelial Lesions (HSIL)

NCT07669363 | Not Yet Recruiting Phase 2

• 1 other identifier: SYSKY-2026-336-03
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 28

Brief Summary

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.

Conditions

Cervical Intraepithelial Neoplasia; Papillomavirus Infections

Keywords

HSIL; High-Grade Squamous Intraepithelial Lesions; CIN2; CIN3; Cervical Intraepithelial Neoplasia; HAL-PDT; Hexaminolevulinate Photodynamic Therapy; Photodynamic Therapy; LEEP; Cold Knife Conization; Cervical Cancer Prevention; Non-inferiority Trial; HPV Clearance

Outcome Measures

Primary Outcomes (1)

• 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)

  12 months after the first treatment

Secondary Outcomes (6)

• Human Papillomavirus (HPV) baseline clearance rate at 6 months

  6 months after the first treatment

• Pathological remission rate at 6 months

  6 months after the first treatment

• HPV baseline clearance rate at 12 months

  12 months after the first treatment

• Quality of life assessed by EORTC QLQ-CX24

  12 months after the first treatment

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  From informed consent through 12 months after the first treatment

Study Arms (2)

Hexaminolevulinate Photodynamic Therapy (HAL-PDT) with Deferred Surgery

EXPERIMENTAL

Subjects receive Hexaminolevulinate Photodynamic Therapy (HAL-PDT) once every 2 weeks (Q2W) for a total of 6 treatment sessions. At 6 months after the first treatment, participants undergo colposcopy-directed cervical biopsy and HPV testing to assess treatment response. Those who achieve pathological remission (normal or LSIL) enter follow-up without surgery. Those who do not achieve remission (persistent HSIL or disease progression) receive standard surgical treatment (LEEP or CKC) within 4 weeks of the 6-month assessment.

Combination Product: HAL 5% with illumination

Immediate Surgery

ACTIVE COMPARATOR

Participants with histologically confirmed HSIL (CIN2 P16 positive/CIN3) receive standard surgical treatment (LEEP or CKC) per routine clinical practice. Follow-up assessments include HPV testing and colposcopy-directed cervical biopsy at 6 months and 12 months post-surgery to evaluate pathological remission and HPV clearance rates. Safety monitoring is conducted from signing of informed consent through the end of study.

Procedure: Loop Electrosurgical Excision Procedure (LEEP) or Cold Knife Conization (CKC)

Interventions

HAL 5% with illumination COMBINATION_PRODUCT

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).

Hexaminolevulinate Photodynamic Therapy (HAL-PDT) with Deferred Surgery

Loop Electrosurgical Excision Procedure (LEEP) or Cold Knife Conization (CKC) PROCEDURE

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.

Immediate Surgery

Eligibility Criteria

• Age: 18 Days+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in this clinical study, fully understand the study content, procedures, and potential adverse reactions, and be able to sign the written informed consent form.
• Able to complete the study in accordance with the study protocol.
• Subject age ≥18 years.
• Presence of High-Grade Squamous Intraepithelial Lesion (HSIL) (CIN2 P16 positive/CIN3), specifically: HSIL with histopathological diagnosis of grade II/III (CIN2 P16 positive/CIN3) within 3 months prior to the first treatment.
• Adequate colposcopy, including: (a) Complete visibility of the cervical transformation zone, including the squamocolumnar junction; (b) Complete visibility of lesion margins.
• The investigator determines that non-surgical treatment is acceptable for the participant.
• The investigator determines that the cervical size is suitable for placement of the HAL-PDT device.
• Meets the following conditions: Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result prior to the start of treatment. No plan for pregnancy during the study period; no sexual activity or use of effective and reliable contraception from the end of the last menstrual period to the start of the study, and agreement to use condoms for barrier contraception during the study period. WOCBP is defined as a female who has experienced menarche, has not undergone hysterectomy or bilateral oophorectomy, and has not reached natural menopause (i.e., no menstruation at all for the past 24 consecutive months).

You may not qualify if:

• Cervical adenocarcinoma in situ or other glandular lesions, invasive cervical cancer, or suspected malignant lesions.
• CIN2 with P16 negative.
• Lesions extending to the vaginal wall, cervical canal, or vaginal fornix, or lesions located on the vulva.
• Prior physical or surgical treatment to the cervix resulting in incomplete cervical structure (e.g., cold knife conization), or receipt of physical or surgical therapy for CIN2 or CIN3 after the current histopathological diagnosis.
• The first study treatment day falls within 7 half-lives of the last antiviral medication.
• Severe pelvic inflammatory disease, severe cervicitis, or other severe gynecological infectious diseases found on colposcopic or clinical examination.
• Investigator judges that vaginal bleeding during treatment may affect treatment outcomes.
• Receipt of any inactivated vaccine within 2 weeks prior to the first treatment, or any live vaccine within 4 weeks prior to the first treatment.
• Previous severe cardiovascular, cerebrovascular, neurological, psychiatric, endocrine, or hematopoietic disease that has not been cured; known severely compromised immune function, or need for long-term use of corticosteroids or immunosuppressants; history of malignancy within 5 years.
• History of clinically significant immunosuppression or confirmed autoimmune disease; or primary immunodeficiency.
• Known or newly identified active sexually transmitted diseases (STDs), including but not limited to HIV, syphilis, genital herpes, unless adequately treated and tested negative before study treatment.
• Presence of a cardiac pacemaker.
• Suspected or known porphyria, or known allergy to the study drug, its chemically similar compounds, or photosensitizers.
• Allergy to silicone.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (28)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350005, China

Location

Xiamen Maternity and Child Healthcare Hospital

Xiamen, Fujian, 361001, China

Location

he First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

Location

The First People's Hospital of Foshan

Foshan, Guangdong, 528000, China

Location

Foshan Shunde Maternal and Child Health Hospital

Foshan, Guangdong, 528300, China

Location

Guangdong Women and Children Hospital

Guangzhou, Guangdong, 510010, China

Location

The Affiliated Cancer Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510095, China

Location

Guangdong ProvincialHospital of Chinese Medicine

Guangzhou, Guangdong, 510120, China

Location

Guangzhou First People's Hospital (The Second Affiliated Hospital of South China University of Technology)

Guangzhou, Guangdong, 510180, China

Location

Zhujiang Hospital, Southern Medical University

Guangzhou, Guangdong, 510280, China

Location

Guangdong Second Provincial GeneralHospital (Guangdong Provincial Emergency Hospital)

Guangzhou, Guangdong, 510317, China

Location

The First AffiliatedHospital, Guangzhou University ofTraditional Chinese Medicine

Guangzhou, Guangdong, 510405, China

Location

Guangzhou Women and Children's Medical Center (The Affiliated Women and Children's Medical Center of Guangzhou Medical University)

Guangzhou, Guangdong, 510623, China

Location

Panyu Central Hospital Affiliated to Guangzhou Medical University

Guangzhou, Guangdong, 511400, China

Location

Shenzhen Maternity and Child Health Hospital

Shenzhen, Guangdong, 518031, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

The First Affiliated Hospital, Sun Yat-sen University

Zhongshan, Guangdong, 510080, China

Location

Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital

Nanning, Guangxi, 530000, China

Location

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

Location

Dongguan Maternal and Child Health Care Hosptial

Dongguan, Guangzhou, 523000, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

The First Affiliated Hospital with Nanjing Medical University (Jiangsu Provincial People's Hospital)

Nanjing, Jiangsu, 210029, China

Location

The First Hospital of Jilin University

Changchun, Jinlin, China

Location

The General Hospital of Northern Theater Command of the Chinese People's Liberation Army

Shenyang, Liaoning, 110016, China

Location

Shanxi Provincial People's Hospital

Taiyuan, Shanxi, 030000, China

Location

The West China Second University Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Papillomavirus Infections; Squamous Intraepithelial Lesions

Interventions

Lighting

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Morphological and Microscopic Findings

Intervention Hierarchy (Ancestors)

Environment, Controlled; Environment; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Gynecologic Oncology

Study Record Dates

• First Submitted: June 21, 2026
• First Posted: June 25, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 16, 2029
• Study Completion (Estimated): June 16, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-07

Locations

CN (28)