Gleolan for Visualization of Newly Diagnosed or Recurrent Ovarian Cancer (OVA-302)

Study Overview
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Brief Summary
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This Phase 3 study is designed to investigate the safety, diagnostic performance, and clinical usefulness of the imaging agent Gleolan (aminolevulinic acid hydrochloride, also referred to as ALA HCl, ALA, 5-ALA), an orally administered imaging agent for the real-time detection and visualization of de novo or recurrent epithelial ovarian cancer during tumor debulking.

Detailed Description
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This Phase 3 study is designed to investigate the safety, diagnostic performance, and clinical usefulness of the imaging agent Gleolan (aminolevulinic acid hydrochloride, also referred to as ALA HCl, ALA, 5-ALA), an orally administered imaging agent for the real-time detection and visualization of de novo or recurrent epithelial ovarian cancer during tumor debulking. Gleolan is a prodrug that is metabolized intracellularly to form the fluorescent molecule Protoporphyrin IX (PpIX). The oral provision of Gleolan leads to a highly selective accumulation of PpIX in tumor cells. Following excitation with blue light (BL) (wavelength [λ] = 375 - 450 nm), the PpIX, which has accumulated selectively in tumor tissue, emits a red-violet light. This phenomenon provides the surgeon with real-time fluorescence (FL) visualization of malignant tissue during cancer resection surgery, which would otherwise not be readily visible to the naked eye. Patients pending resection for suspected epithelial ovarian cancer (Stage I-IV) will sign an informed consent and will be screened to assess study eligibility. Ovarian cancer patients with newly diagnosed disease and those with recurrent disease deemed medically eligible for tumor debulking surgery will be considered for participation. Study participants who are either treatment naïve or have received adjuvant therapy and/or interval debulking and allowed a minimum 21-day waiting period since last treatment are eligible for enrollment. Study participants will be evaluated within 48 hours post-procedure and 2 weeks post-procedure for study safety assessment.

Official Title
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A Phase 3 Multicenter Study of Gleolan™ (Aminolevulinic Acid Hydrochloride) to Enhance Visualization of Tumor in Patients With Suspected Newly Diagnosed or Recurrent Epithelial Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Gleolan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study will be limited to patients with the following diagnoses who plan to undergo surgical cytoreduction or interval debulking: a. primary diagnosis or high clinical suspicion of primary epithelial ovarian cancer, b. suspected epithelial, peritoneal, or fallopian tube cancer, c. recurrent epithelial ovarian cancer. Note: participants with a diagnosis of (a) or (b) may be treatment-naïve or have received neoadjuvant therapy, as clarified in Exclusion Criteria 6 and 9. A pre-operative magnetic resonance image (MRI), positron emission tomography (PET), or computed tomography (CT) ≤ 30 days of study enrollment documenting a suspected tumor or suspected recurrence of tumor for which surgical debulking is indicated and has been planned. Females (only) age ≥ 18 years. Study participants must have normal organ and bone marrow function and be appropriate surgical candidates per site SoC. Study participant must have recording of each parameter as defined below: Bilirubin: Below upper limit of normal AST (SGOT): < 2.5 X institutional upper limit of normal ALT (SGPT): < 2.5 X institutional upper limit of normal Creatinine: Below upper limit of normal OR Creatinine clearance: >60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal The study subject t must demonstrate the ability to understand the informed consent document and the willingness and ability to sign a written informed consent document. The study consent documents will be prepared in English and Spanish. Translation for non-English speaking participants will be provided as appropriate by institution, as required. Women of childbearing potential must agree to use highly effective forms of contraception for at least 42 days after the one-time use of the Gleolan study drug. Exclusion Criteria: Patient is to undergo laparoscopy and their surgeon believes it is unlikely that laparotomy/debulking will occur. Hypersensitivity to aminolevulenic acid (ALA) or porphyrins. Acute or chronic types of porphyria. Uncontrolled concurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness. Patient has had chemotherapy, tumor resection or radiation treatment within 21 days prior to surgery. Social or medical situations that would limit compliance with study requirements (e.g. ability to travel for follow-up or inability to obtain appropriate pre-op MRI, PET, or CT. Women who are pregnant or plan to become pregnant during study participation. Simultaneous participation in another investigational treatment trial in the 21 days directly preceding or after study drug administration. Simultaneous use of other potentially phototoxic substances (e.g., St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines), and topical preparations containing ALA for 24 hours during the perioperative period. Unwillingness by study participant to sign consent or return for subsequent visits following surgery. Any condition that in the opinion of the Investigator would exclude the study participant as a viable candidate for this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients Receiving Gleolan<br>All patients in this arm will receive Gleolan and undergo intraoperative imaging | Drug: Gleolan<br>* Gleolan is a prodrug that is metabolized intracellularly to form the fluorescent molecule Protoporphyrin IX (PpIX). The oral provision of Gleolan leads to a highly selective accumulation of PpIX in tumor cells. Following excitation with blue light (BL) (wavelength [λ] = 375 - 450 nm), the PpIX, which has accumulated selectively in tumor tissue, emits a red-violet light.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the clinical usefulness of Gleolan to detect epithelial ovarian cancer tissue not detected during SoC debulking surgery. | Percentage of participants with at least one suspected ovarian cancer lesion (including lymph nodes) where Gleolan-induced FL is confirmed by central histopathology (Standard of Truth) to be tumor that was not detected during SoC debulking, among all participants who meet the eligibility criteria for the study and receive any amount of Gleolan. | Surgery (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the biopsy-level PPV (i.e., diagnostic performance) of Gleolan for the real-time visualization of newly diagnosed or recurrent epithelial ovarian cancer during debulking surgery. | Positive Predictive Value (PPV) of Gleolan-induced FL among biopsies obtained from each study participant following SoC debulking surgery. | Surgery (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALA, Fluorescence guided surgery, Gleolan, Ovarian cancer