Does immunotherapy for melanoma affect reproductive organs in premenopausal women and men?

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

This study will see if immune checkpoint inhibitor treatment for melanoma changes sex hormone levels and reproductive organ function in adults receiving these drugs.

Quick facts

• Study type: Observational
• Enrollment: 80 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Peter MacCallum Cancer Centre, Australia (other)
• Drugs / interventions: chemotherapy
• Locations: 6 sites (Sydney, New South Wales and 5 other locations)
• Trial ID: NCT07138222 on ClinicalTrials.gov

What this trial studies

This observational study follows adults with Stage II–IV melanoma who are planning to receive immune checkpoint inhibitors and collects clinical data, questionnaires, and biospecimens over 12 months. Blood for gonadal biomarkers will be taken at baseline, 3, 6, and 12 months, with semen samples and testicular measures collected in men at selected timepoints and menstrual/contraceptive history and sexual function questionnaires collected in women. Participants who stop treatment early will have an end-of-treatment assessment within four weeks of stopping. No additional treatments are given and biological samples may be stored for future research with participant consent at Peter MacCallum Cancer Centre.

Who should consider this trial

Good fit: Adults (18+) with Stage II–IV melanoma who are planning to start immune checkpoint inhibitor therapy—particularly premenopausal women (commonly 18–45 with preserved ovarian reserve) and men willing to provide blood and semen samples—are ideal candidates.

Not a fit: People not receiving immune checkpoint inhibitors, postmenopausal individuals, those with a life expectancy under one year, or those unwilling to provide blood or semen samples are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, the results could help patients and clinicians understand and manage possible effects of immunotherapy on fertility and sex hormone function.

How similar studies have performed: While immune checkpoint inhibitors are known to cause various endocrine side effects and there are case reports, systematic human studies specifically measuring gonadal function are limited, so this approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

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

1. Patient has provided written informed consent using the IMPACT Patient Information and Consent form (PICF)
2. Diagnosis of melanoma (Stage II, III or IV) in the de novo or recurrent setting
3. Has a life expectancy of greater than or equal to 1 year
4. 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
5. Age greater than or equal to 18 and less than or equal to 45 years at the time of signing consent
6. 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
7. AMH level greater than or equal to 1.0 pmol/L at registration

   For Cohort 2: men with melanoma
8. Age greater than or equal to 18 and less than or equal to 60 years at the time of signing consent
9. 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:

1. Previous removal of both ovaries (females) or previous removal of both testes or previous vasectomy (males)
2. Planned for or previously had pelvic radiotherapy
3. 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.
4. Previous or concurrent alkylating or platinum-based chemotherapy within the last 2 years
5. Previous use of ICI
6. History of hypogonadism
7. 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

Where this trial is running

Sydney, New South Wales and 5 other locations

• Melanoma Institute Australia — Sydney, New South Wales, Australia (NOT_YET_RECRUITING)
• Princess Alexandra Hospital — Brisbane, Queensland, Australia (NOT_YET_RECRUITING)
• Cairns Base Hospital — Cairns, Queensland, Australia (NOT_YET_RECRUITING)
• Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (RECRUITING)
• The Alfred Hospital — Melbourne, Victoria, Australia (NOT_YET_RECRUITING)
• Austin Hospital — Melbourne, Victoria, Australia (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Dr Wanda Cui, BMEDSCI, MBBS — Peter MacCallum Cancer Centre, Australia
• Study coordinator: Dr Wanda Cui, BMEDSCI, MBBS

Conditions: Melanoma, melanoma, skin cancer, immune checkpoint inhibitors, immunotherapy, gonadal toxicity, ovarian function, testicular function