About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Stage II, III, IV completely resected melanoma
Female sex
Under 40 years of age
Not previously treated with chemotherapy and/or radiotherapy
Disqualifiers
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
Trial 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.
Trial design
Cohort
Prospective
Treatments tested in this trial
Dabrafenib + Trametinib
DrugThere 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
Pembrolizumab
DrugThere 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
Nivolumab
DrugThere 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
Observation
Other interventionPatients who will not initiate adjuvant therapy, but will undergo observation (due to refusal, comorbidities, other reasons).
Treatment groups
Trial outcomes
Primary outcomes
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
Secondary outcomes
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
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
Sponsors and contacts
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