SerUm and Plasma MicroRNAs in Malignant Ovarian gERm Cell Tumours (SUMMER)

The goal of this observational case-control study is to learn about the circulating and tissue microRNA expression, imaging and radiomic profiles of malignant ovarian germ cell tumours (MOGCT) compared to patients with a benign OGCT and no ovarian pathology.

The main question[s] it aims to answer are:

1. To understand the circulating miRNA expression of malignant ovarian germ cell tumours (MOGCTs) compared to those with benign ovarian germ cell tumours (BOGCTs)
2. To understand the imaging profile of MOGCTs compared to that of BOGCTs
3. To establish the relationship between serum and plasma miRNA expression in response to treatment and relapse of disease
4. To discover if miRNA expression correlates with radiomic features of OGCTs on both ultrasound and MRI
5. To see if we can link the micro RNAs in tumour samples to those found in blood samples, and to find a plausible explanation for why these micro RNAs are raised (in terms of the tumour biology itself).aims

Participants will have serial blood tests at different time points in their care to assess how circulating miRNA levels are affected by treatment and/or remission and/or relapse. If they have surgery, a pathology sample will be taken from the main tumour specimen. Radiomic analysis will take place on existing ultrasound images of their mass.

Researchers will compare the circulating miRNA profile of patients with a benign ovarian germ cell tumour and no ovarian pathology to see where the differences lie. If a patient with a BOGCT requires surgery, a pathology sample will be taken from the main tumour specimen. Radiomic analysis will take place on existing ultrasound images of their benign mass.

Study Overview

• Status: Not yet recruiting
• Conditions: Ovarian Neoplasms; Ovarian Cancer; Ovary Cancer; Germ Cell Tumor; Ovary Neoplasm; Germ Cell Cancer; Germ Cell Ovarian Cancer; Germ Cell Neoplasia
• Intervention / Treatment: Diagnostic test: Blood test; Diagnostic test: Pathology specimen miRNA expression

Detailed Description

Case population (MOGCTs):

1. Serum aFP (alpha fetoprotein), hCG (human chorionic gonadotrophin), LDH (lactate dehydrogenase) and Ca125 (cancer antigen 125) tumour markers measured at time of diagnosis
2. Additional serum and plasma sample to be obtained at the same time as initial bloods
3. Subsequent serum and plasma samples to be obtained as per study arms 1-3 based on cancer staging
4. Tissue samples will be obtained at the time of surgery

Control population:

Participants acting as controls will be identified from those attending for TV-USS where either a benign teratoma or no pathology is identified (e.g. from a gynaecology clinic). A total of 26ml of blood will be taken. Serum aFP, hCG, LDH and Ca125 will be measured as per routine clinical practice in patients with a benign OGCT.

Patients in the control population (benign germ cell tumours or patients with no known gynaecological pathology) will have a single blood test for miRNA analysis.

If participants require an operation for the benign GCT, tissue samples will be obtained at the time of surgery.

miRNA analysis will be performed using NanoString for the discovery panel. Further targeted sequencing will be performed in the larger prospective study using specific miRNA panels. This may be done using NanoString or a custom MiRNA assay primer.

Endpoint The pilot will be completed after the final patient has completed 12 months of follow up. The pilot data analysis will take place at that point.

We anticipate that the study will end 12 months after the final participant has completed 24 months of follow up, which gives 12 months for analysis of the samples. The number of participants to take part will be based on a power calculation performed at the time of analysis of the pilot data.

DATA COLLECTION AND MANAGEMENT Patients will enter study arm 1-3 based on cancer staging, or will belong to the control group.

Each participant will be followed up for a maximum of 2 years after they receive their definitive treatment (surgery and/or (neo)adjuvant chemotherapy). We anticipate this will be a maximum of 30 months total time in the study.

An interim analysis of data will be performed at 12 months, with a view to:

1. Identify key miRNAs for prospective validation
2. Allow for appropriate power calculation of the prospective validation study

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Nina C Cooper, MBBS BSc; Phone Number: 02033513150; Email: nina.cooper3@nhs.net
• Study Contact Backup: Name: Srdjan Saso, MRCOG Phd; Phone Number: 02033513150; Email: srdjan.saso01@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women aged over 16 with a diagnosis of a malignant ovarian germ cell tumour, benign ovarian germ cell tumour or no known gynaecological pathology may take part in this study.

Description

Inclusion Criteria:

• All patients with a new diagnosis of a malignant ovarian germ cell tumour.
• The control population will include all patients with a new diagnosis of a benign ovarian germ cell tumour or no known gynaecological pathology.

Exclusion Criteria:

• Previous or ongoing chemotherapy for MOGCT
• Previous surgery for MOGCT
• Pregnancy - this will be verbally communicated for those not having surgery or chemotherapy, for those having surgery or chemotherapy a urine pregnancy test should be negative and documented in the clinical notes.
• Fetal circulating DNA is known to be present in maternal blood and therefore pregnant women should not be included in this study
• Denial of informed consent
• Age <16 years
• History of any other cancer

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases- Malignant Ovarian Germ Cell Tumour - Arm 1; Patients with a diagnosis of stage 1a MOGCT. Bloods taken at the following time points: Day 0, then 4 weeks; 6 months; 12 months; 24 months post-operatively	Diagnostic test: Blood test; Serum and plasma microRNA quantification; Diagnostic test: Pathology specimen miRNA expression; Pathology specimen mirNA expression - ALL MOGCT; OPTIONAL for BOGCT
Cases - Malignant Ovarian Germ Cell Tumour - Arm 2; Patients with a diagnosis of stage 1b/1c MOGCT. Bloods taken at the following time points: Day 0, then 4 weeks; 6 months; 12 months; 24 months post-operatively OR post-final dose of adjuvant chemotherapy	Diagnostic test: Blood test; Serum and plasma microRNA quantification; Diagnostic test: Pathology specimen miRNA expression; Pathology specimen mirNA expression - ALL MOGCT; OPTIONAL for BOGCT
Cases - Malignant Ovarian Germ Cell Tumour - Arm 3; Patients with a diagnosis of stage 2 or higher MOGCT. Bloods taken at the following time points: Day 0, then 4 weeks post-neoadjuvant chemotherapy, then 4 weeks; 6 months; 12 months; 24 months post-operatively	Diagnostic test: Blood test; Serum and plasma microRNA quantification; Diagnostic test: Pathology specimen miRNA expression; Pathology specimen mirNA expression - ALL MOGCT; OPTIONAL for BOGCT
Controls - Benign Ovarian Germ Cell Tumour; Bloods taken at the time of diagnosis of BOGCT (single blood test)	Diagnostic test: Blood test; Serum and plasma microRNA quantification; Diagnostic test: Pathology specimen miRNA expression; Pathology specimen mirNA expression - ALL MOGCT; OPTIONAL for BOGCT
Controls - No Known Gynaecological Pathology; Single blood test	Diagnostic test: Blood test; Serum and plasma microRNA quantification

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in microRNA expression (plasma) between benign and malignant masses	Comparison of heatmaps based on mean expression of clusters across samples	24 months
Difference in microRNA expression (serum) between benign and malignant masses	Comparison of heatmaps based on mean expression of clusters across samples	24 months
microRNA expression (plasma)	Differential expression of microRNAs (assessed using a moderated t statistic and P values adjusted for multiple testing)	24 months
microRNA expression (serum)	Differential expression of microRNAs (assessed using a moderated t statistic and P values adjusted for multiple testing)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative measure of circulating miRNA before treatment	miRNA expression in plasma samples of women with a diagnosis of a MOGCT compared to those of women with BOGCTs using nCounter miRNA Expression panels	24 months
Quantitative measure of circulating miRNA after treatment	miRNA expression in serum samples of women with a diagnosis of a MOGCT compared to those of women with BOGCTs using nCounter miRNA Expression panels	24 months
Quantitative measure of circulating miRNA after treatment	miRNA expression in plasma samples of women with a diagnosis of a MOGCT compared to those of women with BOGCTs using nCounter miRNA Expression panels	24 months
Performance of segmentation model on ultrasound images	Correlation between identification of region of interest (ROI) to examiner segmentation. Dice surface coefficient (DICE).	24 months
Performance of segmentation model on MRI images	Correlation between identification of region of interest (ROI) to examiner segmentation. Dice surface coefficient (DICE)	24 months
Performance of classification model on ultrasound images	Correlation between benign or malignant diagnosis by model vs ultrasound subjective assessment or histopathological diagnosis (area under the ROC curve (AUC), F1-score)	24 months
Performance of classification model on MRI images	Correlation between benign or malignant diagnosis by model vs ultrasound subjective assessment or histopathological diagnosis (area under the ROC curve (AUC), F1-score)	24 months
Quantitative measure of circulating miRNA before treatment	miRNA expression in serum samples of women with a diagnosis of a MOGCT compared to those of women with BOGCTs using nCounter miRNA Expression panels	24 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Srdjan Saso, PhD MRCOG MRCS, Imperial College Healthcare NHS Trust

Study record dates

Study Major Dates

• Study Start (Estimated): April 14, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: March 22, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: microRNA; miRNA; Ovarian Cancer; Germ Cell Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 23CX8477

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No