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

NCT07527819 | Not Yet Recruiting DMC

• 1 other identifier: HREC/123447/PMCC
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 9

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.

Conditions

Triple Negative Breast Cancer (TNBC)

Keywords

Premature Ovarian Insufficiency; chemotherapy; immunotherapy; fertility; immune checkpoint inhibitors; ovarian function; ovarian toxicity; cytokines; inflammation; menopause

Outcome Measures

Primary Outcomes (1)

• Premature Ovarian Insufficiency (POI) at 24 months 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 Outcomes (10)

• Premature Ovarian Insufficiency (POI) at 12 months after cessation of neoadjuvant chemotherapy-ICI

  12 months (±12 weeks) after cessation of neoadjuvant chemotherapy-ICI

• 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

• Change in Menstrual Status

  Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation

• Time to Return of Menses

  Up to 24 months after cessation of treatment

• Change in Oestradiol (E2) Levels

  Baseline; at cessation of treatment; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation

Other Outcomes (2)

• Change in Antral Follicle Count (AFC) and Ovarian Volume

  Baseline; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation of treatment

• Change in Endometrial Thickness

  Baseline; 12 months (±12 weeks); and 24 months (±12 weeks) after cessation of treatment

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (9)

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Mater Hospital Sydney

Sydney, New South Wales, 2060, Australia

Location

Lyell McEwin Hospital

Adelaide, South Australia, 5112, Australia

Location

Icon Cancer Centre

Hobart, Tasmania, 7000, Australia

Location

Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3052, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Washington, 6009, Australia

Location

Related Links

• Peter MacCallum website
• ANZCTR Registration

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood samples will be collected and retained

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Primary Ovarian Insufficiency; Inflammation

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr Wanda Cui, BMEDSCI, MBBS

CONTACT

+61 3 8559 5000; wanda.cui@petermac.org

Kathya Fernando, BBiomedSc

CONTACT

+61 4520 89983; kathya.fernando@petermac.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start: April 8, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

AU (9)