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

Overview

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.

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.

Primary outcome measures

• 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]

Secondary outcome measures (10)

• 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]
• 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]
• Change in Menstrual Status [Time frame: 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]
• Change in Oestradiol (E2) Levels [Time frame: 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 in Inflammatory Cytokine Levels [Time frame: 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]
• Pregnancy Rate and Pregnancy Outcomes [Time frame: Up to 24 months after cessation of treatment]
• Fertility Preservation Discussion and Uptake [Time frame: Baseline (prior to commencement of neoadjuvant chemotherapy-ICI)]

Eligibility criteria

Inclusion criteria

• Patient has provided written informed consent using the FERTILE Patient Information and Consent form (PICF)
• 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 a 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

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Australia · 9 centers

• Chris O'Brien Lifehouse — Camperdown
• Mater Hospital Sydney — Sydney
• Lyell McEwin Hospital — Adelaide
• Icon Cancer Centre — Hobart
• Eastern Health — Box Hill
• Monash Health — Clayton
• Peter MacCallum Cancer Centre — Melbourne
• Royal Melbourne Hospital — Melbourne
• … and 1 more center

Identifiers

NCT: NCT07527819 · HREC/123447/PMCC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗