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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12625001091493
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
17/09/2025
Date registered
Help: Date registered
8/10/2025
Date last updated
Help: Date last updated
9/06/2026
Date data sharing statement initially provided
Help: Data sharing statement date
8/10/2025
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
The FERTILE Study: Evaluating ovarian toxicity outcomes following immunotherapy in patients with Triple-Negative Breast Cancer (TNBC)
Scientific title
The FERTILE Study: Evaluating ovarian toxicity outcomes following immunotherapy in patients with Triple-Negative Breast Cancer (TNBC)
Additional trial identifiers [1] 315400 0
Nil known
Universal Trial Number (UTN)
Trial acronym
FERTILE
Related trial records

Health condition
Health condition(s) studied:
Breast cancer 338904 0
Menopause 338906 0
Fertility 338907 0
Condition category
Condition code
Cancer 335200 335200 0 0
Breast
Reproductive Health and Childbirth 335202 335202 0 0
Menstruation and menopause
Reproductive Health and Childbirth 335289 335289 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of the intervention or exposure
This is a prospective study aiming to describe what happens with the ovarian function and sexual health after receiving chemotherapy and immune checkpoint inhibitor (ICI) treatment as part of standard treatment for triple negative breast cancer in premenopausal woman less than or equal to 42 years.

Chemotherapy and ICI treatment will be delivered regardless of their involvement in the FERTILE study and will be determined by their treating clinician(s).

Eligible patients will be identified by their medical oncologist at one of the participating sites and informed consent will be obtained.

Contraceptive and menstrual history, sexual function questionnaires and blood for biomarkers of ovarian function will be collected at 4 timepoints during the
patient’s routine reviews:
1. Before the first dose of chemotherapy and ICI
2. Within 3 months after breast surgery
3. 12 months after breast surgery
4. 24 months after breast surgery

Patients will also be asked to undergo an optional pelvic ultrasound to count the number of growing follicles (antral follicle count) at the following 3 timepoints:
1. Before the first dose of chemotherapy and ICI
2. 12 months after breast surgery
3. 24 months after breast surgery

As patients with TNBC on chemotherapy and ICI treatment usually have routine clinic visits before treatment commencement, a few weeks after surgery and every year after surgery for surveillance, we aim to collect the additional information, questionnaires, research blood tests and optional ultrasound at the same time as their routine visits.

The anticipated time needed for collection of blood for biomarkers of ovarian function is anticipated to take 10 minutes per visit, completion of contraceptive and menstrual history and sexual function questionnaires is anticipated to take 15-20 minutes per visit, and collection of ultrasound images for antral follicle count is anticipated to take 30 minutes per visit.
Intervention code [1] 332008 0
Not applicable
Description of the comparator or control
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 342811 0
Rates of amenorrhea and post menopausal follicle stimulating hormone (FSH) levels 24 months after surgery for early stage TNBC
Timepoint [1] 342811 0
24 months after surgery
Secondary outcome [1] 452214 0
Rates of amenorrhea and post menopausal FSH levels 12 months after surgery for early stage TNBC
Timepoint [1] 452214 0
12 months after surgery
Secondary outcome [2] 452215 0
Anti-mullerian hormone (AMH) levels before neoadjuvant chemotherapy-ICI, = 3 months of surgery and at 12 and 24 months after surgery for early stage TNBC
Timepoint [2] 452215 0
Before neoadjuvant chemotherapy-ICI, within 3 months and at 12 and 24 months after surgery
Secondary outcome [3] 452216 0
Menstruation before neoadjuvant chemotherapy-ICI, = 3 months of surgery and at 12 and 24 months after surgery for early stage TNBC
Timepoint [3] 452216 0
Before neoadjuvant chemotherapy-ICI, within 3 months and at 12 and 24 months after surgery
Secondary outcome [4] 452217 0
Time to return of menses after surgery for early stage TNBC
Timepoint [4] 452217 0
Before neoadjuvant chemotherapy-ICI, within 3 months and at 12 and 24 months after surgery
Secondary outcome [5] 452218 0
Oestradiol before neoadjuvant chemotherapy-ICI, = 3 months of surgery and at 12 and 24 months after surgery for early stage TNBC
Timepoint [5] 452218 0
Before neoadjuvant chemotherapy-ICI, within 3 months and at 12 and 24 months after surgery
Secondary outcome [6] 452219 0
Sexual function before neoadjuvant chemotherapy-ICI, = 3 months of surgery and at 12 and 24 months after surgery for early stage TNBC
Timepoint [6] 452219 0
Before neoadjuvant chemotherapy-ICI, within 3 months and at 12 and 24 months after surgery
Secondary outcome [7] 452220 0
TNF-alpha, IL-1, IL-6, IFN-gamma and granzyme A and B before neoadjuvant chemotherapy-ICI, = 3 months of surgery and at 12 and 24 months after surgery for early stage TNBC
Timepoint [7] 452220 0
Before neoadjuvant chemotherapy-ICI, = 3 months of surgery and at 12 and 24 months after surgery
Secondary outcome [8] 452221 0
Invasive disease-free survival 12 and 24 months after surgery for early stage TNBC
Timepoint [8] 452221 0
12 and 24 months after surgery
Secondary outcome [9] 452222 0
Rate of pregnancy 24 months after surgery for early stage TNBC
Timepoint [9] 452222 0
24 months after surgery
Secondary outcome [10] 452223 0
Fertility preservation methods discussed prior to commencement of neoadjuvant chemotherapy-ICI treatment for early stage TNBC
Timepoint [10] 452223 0
prior to commencement of neoadjuvant chemotherapy-ICI treatment
Secondary outcome [11] 452526 0
Pregnancy outcomes 24 months after surgery for early stage TNBC
Timepoint [11] 452526 0
24 months after surgery
Secondary outcome [12] 452527 0
Rate of uptake of fertility preservation strategies prior to commencement of neoadjuvant chemotherapy-ICI treatment for early stage TNBC
Timepoint [12] 452527 0
prior to commencement of neoadjuvant chemotherapy-ICI treatment

Eligibility
Key inclusion criteria
1. Patient has provided written informed consent using the FERTILE Patient Information and Consent form (PICF)
2. Early-stage TNBC (definition determined as per clinicians’ discretion)
3. Female patients between 18 and 42 years of age
4. Planned to receive at least one dose of neoadjuvant chemotherapy-ICI with a PD-(L)1 inhibitor including but not limited to pembrolizumab, atezolizumab, durvalumab or nivolumab
5. Planned to receive gonadotrophin releasing hormone (GnRH) agonist with neoadjuvant chemotherapy
Minimum age
18 Years
Maximum age
42 Years
Sex
Females
Healthy volunteers
No
Key exclusion criteria
1. Previous removal of both ovaries or ovarian ablation (such as bilateral ovarian radiotherapy)
2. Patients who have previously received immunotherapy or chemotherapy prior to registration
3. Receiving or planned to receive adjuvant endocrine therapy

Note: patients using GnRH agonist for POI prevention are not excluded

4. Post-menopausal as defined by the investigator
5. History of hypogonadism. Note: Patients with a history of gynaecological conditions such as polycystic ovarian syndrome, endometriosis, adenomyosis, pelvic inflammatory disease, etc., are not excluded
6. 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

Study design
Purpose
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
The primary analysis population is all participants who met all inclusion/exclusion criteria.

A lower-one-sided Wilson 95% confidence limit for the proportion of patients in the primary analysis population with POI at 12 and 24 months post-surgery will be estimated. If this lower limit is greater than 18% at 24 months, we will conclude there is a potential safety signal regarding infertility which needs further investigation.

Missing data will be multiply imputed using chained regression equations, and the Wilson confidence intervals will be pooled using the methods described in Lott {Lott, 2018 #1}.

Changes in ovarian reserve and inflammation from before neoadjuvant chemotherapy-ICI treatment to 24 months after treatment will be reported with 95% confidence intervals as a percentage and absolute change from baseline and modelled using a generalised linear mixed model with an appropriate transformation as required. Invasive disease-free survival up to 12 months post-surgery will be summarised using a Kaplan-Meier curve, with 95% confidence intervals estimated using Greenwoods formula for the standard error.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/04/2026
Actual
28/04/2026
Date of last participant enrolment
Anticipated
31/07/2027
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
75
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 29626 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 29627 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [3] 29628 0
Eastern Health - Box Hill
Recruitment hospital [4] 29629 0
Icon Cancer Centre Hobart - Hobart
Recruitment hospital [5] 29630 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [6] 29631 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [7] 29632 0
Mater Sydney - North Sydney
Recruitment postcode(s) [1] 45966 0
3168 - Clayton
Recruitment postcode(s) [2] 45967 0
2050 - Camperdown
Recruitment postcode(s) [3] 45968 0
3128 - Box Hill
Recruitment postcode(s) [4] 45969 0
7000 - Hobart
Recruitment postcode(s) [5] 45970 0
5112 - Elizabeth Vale
Recruitment postcode(s) [6] 45971 0
6009 - Nedlands
Recruitment postcode(s) [7] 45972 0
2060 - North Sydney

Funding & Sponsors
Funding source category [1] 319989 0
Government body
Name [1] 319989 0
Department of Health, Disability and Aging - Medical Research Future Fund
Country [1] 319989 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
Country
Australia
Secondary sponsor category [1] 322520 0
None
Name [1] 322520 0
Address [1] 322520 0
Country [1] 322520 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318527 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 318527 0
Ethics committee country [1] 318527 0
Australia
Date submitted for ethics approval [1] 318527 0
03/11/2025
Approval date [1] 318527 0
25/02/2026
Ethics approval number [1] 318527 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 144474 0
Dr Wanda Cui
Address 144474 0
Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne Victoria 3000
Country 144474 0
Australia
Phone 144474 0
+61 3 85595000
Fax 144474 0
Email 144474 0
[email protected]
Contact person for public queries
Name 144475 0
Wanda Cui
Address 144475 0
Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne Victoria 3000
Country 144475 0
Australia
Phone 144475 0
+61 3 85595000
Fax 144475 0
Email 144475 0
[email protected]
Contact person for scientific queries
Name 144476 0
Wanda Cui
Address 144476 0
Peter MacCallum Cancer Centre, 305 Grattan Street Melbourne Victoria 3000
Country 144476 0
Australia
Phone 144476 0
+61 3 85595000
Fax 144476 0
Email 144476 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.