FERTILE - [STAGING] Peter MacCallum Cancer Centre

Cancer treatments can cause irreversible damage to the ovaries, resulting in infertility and early menopause.

These treatments may also lead to long-term health effects such as osteoporosis, cardiovascular disease, and cognitive or sexual dysfunction.

Patients are made aware of these risks so they can make informed decisions about their treatment and family planning. However, the impact of newer therapies - like immunotherapy - on ovarian function is not yet fully understood.

One of these immunotherapies - Immune checkpoint inhibitors (ICI) – is commonly used in young breast cancer patients to boost anti-tumour immunity but may also cause systemic inflammation.

Preclinical studies show a 50% reduction in oocyte count in mice treated with ICI, indicating possible fertility impacts. Yet, robust human data is lacking, limiting informed decision making for patients.

As immunotherapy treatments, including ICI, improve cancer outcomes, more patients are living with uncertainty about their fertility and hormonal health.

FERTILE is a cohort study in premenopausal women aged 42 years or under with triple negative breast cancer (TNBC) to assess the impact of chemoimmunotherapy on ovarian function and sexual health.

Dr Wanda Cui is the coordinating principal investigator at the Department of Medical Oncology, Peter MacCallum Cancer Centre (sponsor).

Objectives

In premenopausal women with TNBC:

To estimate the proportion with premature ovarian insufficiency (POI) at 24 months post treatment
To estimate the proportion with premature ovarian insufficiency (POI) at 12 months post treatment
To describe the changes in ovarian reserve (using AMH)
To describe the changes in menstrual pattern
To describe the time for menses to return
To describe the changes in circulating oestradiol
To describe changes in sexual function
To describe changes in inflammation
To describe breast cancer disease outcomes 12 and 24 months after neoadjuvant treatment
To describe pregnancies and pregnancy outcomes
To describe which fertility preservation methods were discussed and their uptake
To describe the changes in ovarian reserve (using antral follicle count [AFC] and ovarian volume)
To describe the changes in endometrial thickness (using ultrasound)

Eligibility criteria

Inclusion criteria

Patients will be eligible for inclusion in this trial if all the following criteria apply:
Patient has provided written informed consent.
Early-stage TNBC (definition determined as per clinicians’ discretion)
Female patients between 18 and 42 years of age
Planned to receive at least one dose of neoadjuvant chemotherapy-ICI with PD-(L)1 inhibitor including but not limited to pembrolizumab, atezolizumab, durvalumab or nivolumab
Planned to receive gonadotrophin releasing hormone (GnRH) agonist with neoadjuvant chemotherapy

Exclusion criteria

Patients will not be eligible for inclusion in this trial if any of the following criteria apply:
Previous removal of both ovaries or ovarian ablation (such as bilateral ovarian radiotherapy)
Patients who have previously received immunotherapy or chemotherapy prior to registration
Receiving or planned to receive adjuvant endocrine therapy
Note: patients using GnRH agonist for POI prevention are not excluded
Post-menopausal as defined by the investigator
Presence of any psychological, social, geographical, or other condition for which, in the opinion of the site Investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Recruitment sites

Recruitment site	State	Site investigator
Peter McCallum Cancer Centre	VIC	Dr Wanda Cui
Eastern Health	VIC	Dr Iris Tung
Monash Health	VIC	Associate Professor Michelle White
Mater Sydney	NSW	Professor Fran Boyle
Chris O’Brien Lifehouse	NSW	Dr Sanjeev Kumar
Sir Charles Gairdner Hospital	WA	Dr Louisa Lo
Icon Cancer Centre Hobart	TAS	Associate Professor Louise Nott
Lyell McEwin Hospital	SA	Associate Professor Rohit Joshi

Funding

This study has been funded under the MRFF 2025.

Project status

Not yet recruiting

Contact

Contact details

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Coordinating Principal Investigator: Dr Wanda Cui
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Clinical Research Coordinator: Kathya Fernando
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More information about this study can be found at Australian New Zealand Clinical Trials Registry.