RecruitingACTRN12625000395437

IMmune checkPoint inhibitor related gonAdal toxiCiTy in premenopausal women and men with melanoma – the IMPACT study

Sponsor

Peter MacCallum Cancer Centre

Enrollment

80 participants

Start Date

Aug 5, 2025

Study Type

Observational

Conditions

Melanoma Menopause Hypogonadism

Summary

This study aims to capture information regarding the effect of immune checkpoint inhibitor (ICI) treatment for melanoma on reproductive organ function and sex hormone levels. Who is it for? You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with melanoma (Stage II, III or IV) and you are planning to receive ICI treatment. Additional criteria will apply dependent upon your biological sex characteristics. Study details All participants who choose to enrol in this study will be asked to complete a series of questionnaires and provide blood at 4 of their scheduled treatment visits. These visits are anticipated to add 30 minutes to the scheduled visit time. Male participants will also be asked to provide semen samples at 2 of their scheduled treatment visits. These visits are anticipated to add an additional 30 minutes to the scheduled visit time. No additional or novel treatments will be offered to participants who choose to enrol in this study, this is an observational study only. It is hoped this research will contribute important information regarding the potential toxic effects of ICI treatment on sexual and reproductive function in patients with melanoma who are receiving ICI treatment.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria14

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 Criteria8

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

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Interventions

This is a prospective study aiming to describe what happens with the gonadal function after receiving immune checkpoint inhibitor (ICI) treatment as part of standard treatment for melanoma in two cohorts of patients: 1) premenopausal woman less than or equal to 45 years and 2) men less than or equal to 60 years. ICI treatment will be delivered regardless of their involvement in the IMPACT study and will be determined by their treating clinician(s). Eligible patients will be identified by their medical oncologist at one of the participating sites and informed consent will be obtained. Contraceptive and menstrual history, sexual function questionnaires and blood for biomarkers of ovarian and testicular function will be collected at 4 timepoints during the patient’s routine treatment reviews for both cohorts: 1. Before the first dose of ICI 2. 3 months after commencing ICI 3. 6 months after commencing ICI 4. 12 months after commencing ICI In men (cohort 2), semen will also be collected 1. Before first dose of ICI 2. 6 months after commencing ICI In a subset of men (cohort 2), testicular volume will also be collected using an orchidometer 1. Before first dose of ICI 2. 6 months after commencing ICI For participants in both cohorts who discontinue ICI before 12 months, questionnaires and blood will be collected within 4 weeks after last ICI dose. As patients on ICI treatment usually have routine clinic visits and blood tests taken during treatment to make sure they are not having any side effects, we aim to collect the additional information, questionnaires and research blood tests at the same time as their routine visits and blood tests. The anticipated time needed for collection of blood for biomarkers of ovarian and testicular function is anticipated to take 10 minutes per visit, completion of contraceptive and menstrual history and sexual function questionnaires is anticipated to take 15-20 minutes per visit, collection of semen for semen analysis is anticipated to take 30 minutes per visit and measurement of testicular volume using an orchidometer is anticipated to take 10 minutes per visit.