IMmune checkPoint Inhibitor Related gonAdal toxiCiTy in Premenopausal Women and Men With Melanoma

While immune checkpoint inhibitors (ICIs) are widely used in young melanoma patients and may cause immune-related side effects, their impact on human gonadal function is unknown.

Eligible patients will be identified by their oncologist and provide informed consent. Menstrual/contraceptive history, sexual function questionnaires, and blood samples for gonadal biomarkers will be collected at baseline, 3, 6, and 12 months. Semen and testicular volume (in a subset) will be assessed in men at baseline and 6 months. Patients who cease ICI before the 12 month timepoint will have also have an end of treatment assessment within 4 weeks of stopping treatment.

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.

Inclusion criteria

Patients will be eligible for inclusion in this trial if all the following criteria apply:

• Patient has provided written informed consent using the IMPACT Patient Information and Consent form (PICF)
• Diagnosis of melanoma (Stage II, III or IV) in the de novo or recurrent setting
• Has a life expectancy of greater than or equal to 1 year
• Planned to receive ICI treatment, either in the neoadjuvant, adjuvant or metastatic setting, including as:

• Monotherapy
• Combination therapy

For cohort 1: premenopausal women with melanoma

• Age greater than or equal to 18 and less than or equal to 45 years at the time of signing consent
• Patient is premenopausal (defined as baseline FSH within the premenopausal range per local laboratory at registration). Women on hormonal contraception who have an abnormal FSH level, will be included if their AMH level is greater than or equal to 1.0 pmol/L at registration
• AMH level greater than or equal to 1.0 pmol/L at registration

For Cohort 2: men with melanoma

• Age greater than or equal to 18 and less than or equal to 60 years at the time of signing consent
• Fasting morning total testosterone, LH and FSH within the normal range (per local laboratory) at the time registration

Exclusion criteria

Patients will not be eligible for inclusion in this trial if any of the following criteria apply:

• Previous removal of both ovaries (females) or previous removal of both testes or previous vasectomy (males)
• Planned for or previously had pelvic radiotherapy
• Any medications within the prior 6 months known to disrupt the hypothalamic pituitary gonadal axis, e.g., GnRH agonists or antagonists, selective estrogen receptor modulators (SERMs), aromatase inhibitors, testosterone, anabolic steroids, etc.
• Previous or concurrent alkylating or platinum-based chemotherapy within the last 2 years
• Previous use of ICI
• History of hypogonadism
• 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