Overcoming Chemoresistance in Advanced Ovarian Cancer Via Targeting Hypoxia

Study Overview
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Brief Summary
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The goal of this non-randomized prospective study is to use 18F-EF5-PET/CT imaging to identify and locate intraabdominal hypoxic ovarian cancer lesions. With targeted surgical sampling, precisely obtain hypoxic and potentially chemoresistant cancer tissue for our analyses and identify key molecular differences between hypoxic and non-hypoxic tumors within the same patient. A portion of advanced stage EOC are inoperable at diagnosis and can be treated with neoadjuvant chemotherapy (NACT) before surgery. This approach offers a unique opportunity to study how hypoxic tumor areas respond to treatment.

Detailed Description
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MORE SPECIFIC AIMS To validate the feasibility of PET-tracer EF5 in EOC imaging. Quantify the amount and exact locations of hypoxic tumors in EOC patients using herein developed protocol and tracers (18F-EF5 and 18F-FDG) in diagnostic and neoadjuvant settings. Measure the non-cancer related EF5 accumulation spots and establish the potential pitfalls in abdominal EF5 imaging Establish a method to verify hypoxic locations with 18F-EF5-PET/CT information during the operation. Develop and validate a model that predicts chemotherapy response based on functional imaging information. To reveal hypoxia related alterations in collected tissue samples (i.e. altered DNA damage repair, altered mitochondrial respiratory functioning, overexpression of hypoxia response elements etc)

Official Title
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Overcoming Chemoresistance in Advanced Ovarian Cancer Via Targeting Hypoxia

Conditions
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Epithelial Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Carcinoma, Hypoxia

Intervention / Treatment
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* Device: Imaging with 18F-EF5 PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed advanced epithelial ovarian, primary peritoneal or fallopian tube cancer. age 18-79 years informed concent Exclusion Criteria: previous cancer pregnancy or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDS<br>18F-EF5 PET/CT and 18F-FDG PET/CT scan prior to primary cytoreductive surgery and targeted sample collection during primary cytoreductive surgery | Device: Imaging with 18F-EF5 PET/CT<br>* Both 18F-FDG PET/CT and 18F-EF5 PET/CT imaging are performed in 1) preoperative work-up to clarify the disease distribution, 2) before IDS to evaluate treatment response to NACT (IDS arm); targeted samples from hypoxic and non-hypoxic tumors are collected during surgery<br>* Other names: Collection of targeted samples during surgery;|
| Experimental: IDS<br>18F-EF5 PET/CT and 18F-FDG PET/CT scans prior to diagnostic laparoscopy and after neoadjuvant chemotherapy before interval cytoreductive surgery . Targeted sample collection during diagnostic laparoscopy and interval cytoreductive surgery | Device: Imaging with 18F-EF5 PET/CT<br>* Both 18F-FDG PET/CT and 18F-EF5 PET/CT imaging are performed in 1) preoperative work-up to clarify the disease distribution, 2) before IDS to evaluate treatment response to NACT (IDS arm); targeted samples from hypoxic and non-hypoxic tumors are collected during surgery<br>* Other names: Collection of targeted samples during surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18F-EF5 maximum standardized uptake values (SUVmax) | Tumor and musculus gluteus maximus SUVmax ratio ≥1.5 is considered to refer to hypoxia | 2-3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between the uptake of 18F-EF5 isotope in PET/CT and immunohistochemical profile of tumor tissue |  | 2-3 years | 
| Disease-free survival |  | 5 years | 
| Overall survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced ovarian cancer, EF5-PET/CT, hypoxia