Evaluating Ovarian Toxicity Outcomes Following Immunotherapy in Patients With Triple-Negative Breast Cancer (TNBC) (FERTILE)

April 7, 2026 updated by: Peter MacCallum Cancer Centre, Australia

This study aims to collect information about the effects of chemotherapy combined with immunotherapy (immune checkpoint inhibitors) for early-stage triple-negative breast cancer (TNBC) on ovarian function and fertility.

You may be eligible for this study if you have been diagnosed with early-stage TNBC and are planning to receive neoadjuvant chemotherapy combined with immunotherapy before surgery. Additional eligibility criteria apply.

Participants who choose to enroll will be asked to complete questionnaires and provide blood samples before and after treatment to measure hormone levels related to ovarian function. Information about menstrual patterns, fertility preservation discussions, and reproductive health will also be collected. Some participants may undergo ultrasound assessments to evaluate ovarian reserve and endometrial thickness. Follow-up will continue for up to 24 months after treatment to assess long-term ovarian function.

No additional or experimental cancer treatments will be provided as part of this study. This is an observational study only, and participants will receive standard cancer treatment as recommended by their treating team.

It is hoped this research will provide important information about the potential effects of chemotherapy and immunotherapy on ovarian health and fertility in women receiving treatment for early-stage TNBC.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Patients will be asked to consent to the future use of their biological samples collected during the trial. Samples will be securely stored at Peter MacCallum Cancer Centre, coded, and linked to clinical data. Patients can request sample destruction at any time, but past analyses cannot be undone.

The Sponsor or delegate will manage trial data, while sites are responsible for data entry and resolving queries. Data will be entered into REDCap, a secure system hosted by Peter MacCallum Cancer Centre. Site staff will be trained, and only authorized personnel listed on the delegation log may complete eCRFs.

Study Type

Observational

Enrollment (Estimated)

75

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
        • Contact:
        • Principal Investigator:
          • Dr Sanjeev Kumar
      • Sydney, New South Wales, Australia, 2060
    • South Australia
      • Adelaide, South Australia, Australia, 5112
        • Lyell McEwin Hospital
        • Contact:
        • Principal Investigator:
          • A/Prof Rohit Joshi
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
    • Victoria
      • Box Hill, Victoria, Australia, 3128
      • Clayton, Victoria, Australia, 3168
        • Monash Health
        • Contact:
        • Principal Investigator:
          • A/Prof Michelle White
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
        • Contact:
        • Principal Investigator:
          • Dr Wanda Cui
      • Melbourne, Victoria, Australia, 3052
        • Royal Melbourne Hospital
        • Contact:
        • Principal Investigator:
          • Dr Wanda Cui
    • Washington
      • Nedlands, Washington, Australia, 6009

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with early-stage TNBC who meet all the inclusion and none of the exclusion criteria will be eligible for the study.

Description

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

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. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Premenopausal Women With Early-Stage Triple-Negative Breast Cancer

Premenopausal women aged 18-42 years with newly diagnosed early-stage triple-negative breast cancer (TNBC) who are scheduled to receive standard-of-care neoadjuvant chemotherapy in combination with an immune checkpoint inhibitor (ICI). Participants must have at least one ovary in situ and no prior systemic therapy for their current breast cancer diagnosis.

All participants will undergo serial clinical, biochemical, and patient-reported assessments of ovarian function from baseline (prior to treatment initiation) through 24 months following cessation of neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Premature Ovarian Insufficiency (POI) at 24 months after cessation of neoadjuvant chemotherapy-ICI
Time Frame: 24 months (±12 weeks) after cessation of neoadjuvant chemotherapy-ICI
Proportion of participants with at least one ovary in situ who meet criteria for premature ovarian insufficiency (POI), defined as amenorrhoea for ≥4 months and post-menopausal follicle-stimulating hormone (FSH) level >25 IU/L.
24 months (±12 weeks) after cessation of neoadjuvant chemotherapy-ICI

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Premature Ovarian Insufficiency (POI) at 12 months after cessation of neoadjuvant chemotherapy-ICI
Time Frame: 12 months (±12 weeks) after cessation of neoadjuvant chemotherapy-ICI
Proportion of participants with at least one ovary in situ who meet criteria for POI, defined as amenorrhoea for ≥4 months and post-menopausal FSH level >25 IU/L.
12 months (±12 weeks) after cessation of neoadjuvant chemotherapy-ICI
Change in Anti-Müllerian Hormone (AMH) Levels
Time Frame: Baseline; at cessation of treatment (within 12 weeks of last dose); 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Absolute and percentage change in serum AMH levels from baseline to end of neoadjuvant chemotherapy-ICI, 12 months, and 24 months post-treatment cessation.
Baseline; at cessation of treatment (within 12 weeks of last dose); 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Change in Menstrual Status
Time Frame: Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Change in menstrual pattern (including amenorrhoea, oligomenorrhoea, or regular menstruation) compared to baseline, assessed by participant report.
Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Time to Return of Menses
Time Frame: Up to 24 months after cessation of treatment
Time from cessation of neoadjuvant chemotherapy-ICI to first reported menstrual period in participants who experienced treatment-related amenorrhoea.
Up to 24 months after cessation of treatment
Change in Oestradiol (E2) Levels
Time Frame: Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Absolute and percentage change in serum oestradiol levels from baseline to subsequent study timepoints.
Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Change in Sexual Function (EORTC QLQ-SH22 Score)
Time Frame: Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Change from baseline in sexual function and symptom scores measured using the European Organisation for Research and Treatment of Cancer Sexual Health Questionnaire (EORTC QLQ-SH22).
Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Change in Inflammatory Cytokine Levels
Time Frame: Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Absolute and percentage change in circulating inflammatory cytokines (TNF-α, IL-1, IL-6, IFN-γ, granzyme A and B) from baseline, and association with POI at 24 months.
Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation
Invasive Disease-Free Survival
Time Frame: 12 months and 24 months after cessation of treatment
Time from cessation of neoadjuvant chemotherapy-ICI to invasive breast cancer recurrence or death from any cause.
12 months and 24 months after cessation of treatment
Pregnancy Rate and Pregnancy Outcomes
Time Frame: Up to 24 months after cessation of treatment
Proportion of participants who achieve pregnancy and description of pregnancy outcomes (e.g., live birth, miscarriage, termination).
Up to 24 months after cessation of treatment
Fertility Preservation Discussion and Uptake
Time Frame: Baseline (prior to commencement of neoadjuvant chemotherapy-ICI)
Proportion of participants who report fertility preservation counselling prior to treatment initiation and proportion who undergo fertility preservation procedures.
Baseline (prior to commencement of neoadjuvant chemotherapy-ICI)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Antral Follicle Count (AFC) and Ovarian Volume
Time Frame: Baseline; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation of treatment
Change from baseline in antral follicle count and ovarian volume measured by transvaginal ultrasound in consenting participants.
Baseline; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation of treatment
Change in Endometrial Thickness
Time Frame: Baseline; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation of treatment
Change from baseline in endometrial thickness measured by transvaginal ultrasound in consenting participants.
Baseline; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peter MacCallum Cancer Centre, Australia

Collaborators

Eastern Health
Sir Charles Gairdner Hospital
Monash Health
Lyell McEwin Hospital
Hunter Medical Research Institute (HMRI)
Royal Melbourne Hospital, Australia
Mater Hospital Sydney
Chris O'Brien Lifehouse
Icon Cancer Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 8, 2026

Primary Completion (Estimated)

April 1, 2031

Study Completion (Estimated)

December 31, 2031

Study Registration Dates

First Submitted

April 7, 2026

First Submitted That Met QC Criteria

April 7, 2026

First Posted (Actual)

April 14, 2026

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HREC/123447/PMCC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Maybe requested for future research.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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