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

September 4, 2025 updated by: Intergruppo Melanoma Italiano

MELAFERT: Impact of Adjuvant Therapy on FERTility in Patients With Resected MELAnoma at High Risk of Relapse. A Prospective Multicenter Observational Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

270

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Bari, Italy, 70122
        • Not yet recruiting
        • Ospedale Oncologico "Giovanni Paolo II"
        • Contact:
      • Genova, Italy
        • Not yet recruiting
        • IRCCS Ospedale Policlinico San Martino, Oncologia Medica 2
        • Contact:
      • Milan, Italy, 20861
      • Modena, Italy, 41125
      • Napoli, Italy, 80016
        • Not yet recruiting
        • Istituto Nazionale Tumori "Fondazione PASCALE"
        • Contact:
      • Padua, Italy, 35128
        • Not yet recruiting
        • IOV Istituto Oncologico Veneto
        • Contact:
      • Perugia, Italy, 06132
        • Recruiting
        • Azienda Ospedaliera Santa Maria della Misericordia - Unità di Oncologia Medica.
        • Contact:
      • Roma, Italy, 00168
        • Not yet recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
      • Siena, Italy, 53035
        • Not yet recruiting
        • Università degli Studi di Siena - U.O.C. Immunoterapia Oncologica Azienda Ospedaliera Universitaria Senese
        • Contact:
      • Torino, Italy, 10126
        • Not yet recruiting
        • Università di Torino - Clinica Dermatologica
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Reproductive-age female patients with completely resected stage II, III, IV melanoma, irrespective of BRAF mutational status, with no previous history of chemo, radiation therapy and/or ovarian surgery.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort A
BRAF/MEK inhibitors
Drug: Dabrafenib + Trametinib
There is no different use in the clinical application of the drugs reported above, the study on fertility will be implemented in the women with completely resected melanoma enrolled in the study
Cohort B
Anti-PD-1
Drug: Pembrolizumab
There is no different use in the clinical application of the drugs reported above, the study on fertility will be implemented in the women with completely resected melanoma enrolled in the study
Drug: Nivolumab
There is no different use in the clinical application of the drugs reported above, the study on fertility will be implemented in the women with completely resected melanoma enrolled in the study
Cohort C
Observation arm
Other: Observation
Patients who will not initiate adjuvant therapy, but will undergo observation (due to refusal, comorbidities, other reasons).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
serum antimullerian hormone (AMH)
Time Frame: 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
18 months after the start of therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: • 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
• AMH at 3 months after the start of adjuvant therapy • AMH at 12 months after the start of adjuvant therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Intergruppo Melanoma Italiano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 4, 2025

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

August 1, 2032

Study Registration Dates

First Submitted

July 22, 2025

First Submitted That Met QC Criteria

July 22, 2025

First Posted (Actual)

July 30, 2025

Study Record Updates

Last Update Posted (Estimated)

September 5, 2025

Last Update Submitted That Met QC Criteria

September 4, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MELAFERT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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