Evaluation of 5-Aminolevulinic Acid Hydrochloride for Intraoperative Imaging in Ovarian Cancer Detection: A Single-Center Feasibility Study

The primary objective of this study is to evaluate the **efficacy** of intraoperative imaging using 5-Aminolevulinic Acid (5-ALA) in detecting ovarian cancer tumor manifestations that would not have been identified by normal light and palpation and would not have been scheduled for resection. This is clinically relevant as it may enhance the detection of otherwise undetectable tumor sites, potentially improving surgical outcomes and patient prognosis in ovarian cancer management.

Secondary objectives include evaluating the application of intraoperative imaging using 5-ALA in terms of:

• **Safety**
• Positive predictive value
• Sensitivity
• Patient-related false positive rate
• Lesion-related false positive rate
• Peritoneal Cancer Index (PCI)

The clinical trial focuses on evaluating the efficacy of intraoperative imaging using 5-ALA in detecting **ovarian cancer** tumor manifestations. The study population consists exclusively of female participants aged 18 years and older, with either confirmed or suspected ovarian cancer or recurrence. Participants are required to have planned surgical treatment by staging or debulking laparotomy, including interval debulking operations after previous neoadjuvant chemotherapy. The trial does not include male subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. Key inclusion criteria include obtaining written informed consent in accordance with local regulations and ethical review board standards.

The clinical trial is designed to evaluate the efficacy of **5-aminolevulinic acid hydrochloride** for intraoperative imaging in patients with **ovarian cancer**. This is a Phase IV, single-center feasibility study with a randomized, double-blind, controlled design. The trial is expected to commence on November 1, 2024, and conclude by June 30, 2026. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the percentage of patients with at least one 5-ALA positive and histologically positive ovarian cancer tumor manifestation not scheduled for resection under standard conditions.

The study will begin with an inclusion visit, where participants will undergo screening to ensure they meet the principal inclusion criteria, such as being female, aged 18 years or older, and having confirmed or suspected ovarian cancer. Following the inclusion visit, participants will receive the investigational product, Gliolan 30 mg/ml powder for oral solution, administered orally. The trial will include follow-up visits to monitor the safety and efficacy of the treatment, with assessments of adverse reactions and perioperative morbidity. The end-of-study visit will mark the conclusion of the participant's involvement, where final evaluations will be conducted.

Participants may be withdrawn from the study if they experience severe adverse reactions or if they no longer meet the inclusion criteria. The study aims to provide valuable insights into the potential of 5-ALA in enhancing the detection of ovarian cancer tumor manifestations during surgery, thereby improving surgical outcomes. The trial will adhere to ethical standards and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the use of **Gliolan 30 mg/ml powder for oral solution**, which contains the active substance **aminolevulinic acid hydrochloride**. This experimental medication is administered as an **oral solution**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 20 mg/kg. The administration is conducted orally, and the treatment period is limited to a single day. The pharmaceutical form of the medication is a powder that is reconstituted into an oral solution prior to administration. The active substance, aminolevulinic acid hydrochloride, is of chemical origin and is utilized for its properties in enhancing intraoperative imaging.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are employed. The focus is solely on evaluating the efficacy of the experimental medication in detecting ovarian cancer tumor manifestations during surgery. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to assess the potential of 5-ALA in improving the visualization of tumors that are not easily identified through conventional methods.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the percentage of patients with at least one **5-ALA** positive and histologically positive ovarian cancer tumor manifestation that was not scheduled for resection based on the surgical plan established under standard conditions, which include normal light and palpation. This endpoint aims to determine the effectiveness of intraoperative imaging using **5-ALA** in detecting ovarian cancer manifestations that would otherwise remain undetected.

Secondary endpoints include the assessment of active-substance-specific adverse reactions and serious adverse reactions of CTCAE grades 3, 4, and 5, as well as perioperative morbidity within 30 days. This will be compared with historical data on perioperative morbidity at the study site using the Memorial Sloan Kettering Cancer Center (MSKCC) Surgical Secondary Events (SSE) system. Additional secondary endpoints involve the proportion of **5-ALA** positive and histologically positive lesions out of all **5-ALA** positive lesions, the proportion of **5-ALA** positive and histologically positive lesions out of all histologically positive lesions, and the proportion of patients in whom all **5-ALA** positive lesions are histologically negative. Furthermore, the trial will assess the proportion of **5-ALA** positive but histologically negative lesions among all **5-ALA** positive lesions only, the change in Peritoneal Cancer Index (PCI) by considering additionally resected **5-ALA** positive and histologically confirmed ovarian cancer tumor manifestations, and the change in FIGO classification considering these additionally resected manifestations.