NCT07092670

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
270

participants targeted

Target at P75+ for all trials

Timeline
76mo left

Started Aug 2025

Longer than P75 for all trials

Geographic Reach
1 country

10 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress11%
Aug 2025Aug 2032

First Submitted

Initial submission to the registry

July 22, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 30, 2025

Completed
5 days until next milestone

Study Start

First participant enrolled

August 4, 2025

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2028

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2032

Last Updated

September 5, 2025

Status Verified

September 1, 2025

Enrollment Period

3 years

First QC Date

July 22, 2025

Last Update Submit

September 4, 2025

Conditions

Keywords

MELANOMAfertilityskin cancer

Outcome Measures

Primary Outcomes (1)

  • serum antimullerian hormone (AMH)

    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 Outcomes (1)

  • 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

Study Arms (3)

Cohort A

BRAF/MEK inhibitors

Drug: Dabrafenib + Trametinib

Cohort B

Anti-PD-1

Drug: PembrolizumabDrug: Nivolumab

Cohort C

Observation arm

Other: Observation

Interventions

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 A

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

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

Patients who will not initiate adjuvant therapy, but will undergo observation (due to refusal, comorbidities, other reasons).

Cohort C

Eligibility Criteria

AgeUp to 40 Years
Sexfemale(Gender-based eligibility)
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-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.

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Ospedale Oncologico "Giovanni Paolo II"

Bari, 70122, Italy

NOT YET RECRUITING

IRCCS Ospedale Policlinico San Martino, Oncologia Medica 2

Genova, Italy

NOT YET RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20861, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria, Modena

Modena, 41125, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori "Fondazione Pascale"

Napoli, 80016, Italy

NOT YET RECRUITING

IOV Istituto Oncologico Veneto

Padua, 35128, Italy

NOT YET RECRUITING

Azienda Ospedaliera Santa Maria della Misericordia - Unità di Oncologia Medica.

Perugia, 06132, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

NOT YET RECRUITING

Università degli Studi di Siena - U.O.C. Immunoterapia Oncologica Azienda Ospedaliera Universitaria Senese

Siena, 53035, Italy

NOT YET RECRUITING

Università di Torino - Clinica Dermatologica

Torino, 10126, Italy

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum antimullerian hormone (AMH), Follicle Stimulating Hormone (FSH), 5-beta oestradiol

MeSH Terms

Conditions

MelanomaSkin Neoplasms

Interventions

dabrafenibtrametinibpembrolizumabNivolumabObservation

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsMethodsInvestigative Techniques

Central Study Contacts

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 22, 2025

First Posted

July 30, 2025

Study Start

August 4, 2025

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

August 1, 2032

Last Updated

September 5, 2025

Record last verified: 2025-09

Locations