MELAFERT: Impact of Adjuvant Therapy on FERTility in Patients With Resected MELAnoma at High Risk of Relapse.

Recruiting

• Conditions: Melanoma; Fertility
• Interventions: Drug: Dabrafenib + Trametinib; Drug: Pembrolizumab; Other: Observation; Drug: Nivolumab

• Registration Number: NCT07092670
• Lead Sponsor: Mario Mandalà

Brief Summary

Melanoma survivorship in reproductive-age women is increasing due to the advent of effective therapies in the curative setting. However, while the impact on fertility and ovarian function of chemotherapy agents is well known, there is still a lack of consistent data regarding novel the Mitogen-activated protein kinase (MAP) kinase pathway inhibitors and immune-checkpoint inhibitors (ICIs) used in melanoma.

A recent study showed that a single course of anti-PD-1 (PD, Programmed cell death protein 1) or anti-CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) reduced both the number and quality of oocytes in mice through an immune-mediated mechanism. In particular, primordial follicle damage cannot be restored, leading to relevant clinical implications.

The study aims to help to determine the impact of MAP kinase pathway inhibitors and ICIs on reproductive outcomes, and whether clinicians should discuss (and in what terms) fertility preservation techniques in reproductive-age women receiving ICIs and MAP kinase pathway inhibitors in the adjuvant setting.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-07-22
• Study First Submitted QC: 2025-07-22
• Study First Posted: 2025-07-30
• Status Verified: 2025-08
• Study Start: 2025-08-01
• Last Update Submitted: 2025-08-08
• Last Update Posted: 2025-08-13
• Primary Completion: 2028-08-01
• Study Completion: 2032-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 270

Inclusion Criteria

1. Stage II, III, IV completely resected melanoma
2. Female sex
3. Under 40 years of age
4. Not previously treated with chemotherapy and/or radiotherapy
5. Being able to give written informed consent.

Exclusion Criteria

1. Unresectable melanoma
2. Predisposing conditions for infertility
3. Early menopause or family history of early ovarian failure (idiopathic, < 45 years)
4. Previous bilateral ovariectomy or other ovarian surgery
5. Personal history of autoimmune diseases, endocrine disorders (except for hypothyroidism)
6. Personal history of severe mental disorders associated with infertility (e.g., nervous anorexia) and/or requiring treatments that could impair fertility
7. Inability to give written informed consent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort A	Dabrafenib + Trametinib	BRAF/MEK inhibitors
Cohort B	Pembrolizumab	Anti-PD-1
Cohort B	Nivolumab	Anti-PD-1
Cohort C	Observation	Observation arm

Primary Outcome Measures

Name	Time	Method
serum antimullerian hormone (AMH)	18 months after the start of therapy	To evaluate, in women of childbearing age, the variation in ovarian reserve after completion of adjuvant therapy with BRAF/MEK inhibitors or anti-PD-1 agents

Secondary Outcome Measures

Name	Time	Method
To assess long-term fertility preservation after completion of adjuvant therapy To assess the early impact on fertilitY preservation of a short course of therapy	• AMH at 3 months after the start of adjuvant therapy • AMH at 12 months after the start of adjuvant therapy	correlation between baseline/post-treatment serum AMH and pregnancy rate correlation between baseline/post-treatment serum AMH and menstrual activity ratio between desired (Gd)/ obtained (Go) pregnancies other reproductive outcomes

Trial Locations

Locations (10)

IRCCS Ospedale Policlinico San Martino, Oncologia Medica 2; 🇮🇹 Genova, Italy

Ospedale Oncologico "Giovanni Paolo II"; 🇮🇹 Bari, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Azienda Ospedaliero-Universitaria, Modena; 🇮🇹 Modena, Italy

Istituto Nazionale Tumori "Fondazione Pascale"; 🇮🇹 Napoli, Italy

IOV Istituto Oncologico Veneto; 🇮🇹 Padova, Italy

Azienda Ospedaliera Santa Maria della Misericordia - Unità di Oncologia Medica.; 🇮🇹 Perugia, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

Università degli Studi di Siena - U.O.C. Immunoterapia Oncologica Azienda Ospedaliera Universitaria Senese; 🇮🇹 Siena, Italy

Università di Torino - Clinica Dermatologica; 🇮🇹 Torino, Italy