Triple Negative Breast Cancer (TNBC)
Conditions
Keywords
Premature Ovarian Insufficiency, chemotherapy, immunotherapy, fertility, immune checkpoint inhibitors, ovarian function, ovarian toxicity, cytokines, inflammation, menopause
Brief summary
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.
Interventions
None listed
Sponsors
Peter MacCallum Cancer Centre, Australia
Hunter Medical Research Institute (HMRI)
Royal Melbourne Hospital, Australia
Monash Health
Eastern Health
Mater Hospital Sydney
Chris O'Brien Lifehouse
Lyell McEwin Hospital
Sir Charles Gairdner Hospital
Icon Cancer Centre
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 42 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Premature Ovarian Insufficiency (POI) at 24 months after cessation of neoadjuvant chemotherapy-ICI | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Premature Ovarian Insufficiency (POI) at 12 months after cessation of neoadjuvant chemotherapy-ICI | 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. |
| Change in Anti-Müllerian Hormone (AMH) Levels | 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. |
| Change in Menstrual Status | 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. |
| Time to Return of Menses | 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. |
| Change in Oestradiol (E2) Levels | 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. |
| Change in Sexual Function (EORTC QLQ-SH22 Score) | 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). |
| Change in Inflammatory Cytokine Levels | 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. |
| Invasive Disease-Free Survival | 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. |
| Pregnancy Rate and Pregnancy Outcomes | 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). |
| Fertility Preservation Discussion and Uptake | 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. |
Countries
Australia
Contacts
CONTACTDr Wanda Cui, BMEDSCI, MBBS
CONTACTKathya Fernando, BBiomedSc
Outcome results
None listed