Our proposal is to conduct an open phase II clinical trial that allows us to explore the activity of ketoconazole, an inhibitor of the enzyme CYP17, in ovarian granulosa tumors similar to what has been done in prostate cancer. The rational is based on dysregulation that FOXL2 mutations present in almost all granulosa tumors result in the expression of CYP17 that appears to be key in the development and progression of the disease. This work would represent the first attempt to address the treatment of ovarian granulosa cancer with a molecular solid rational, drawing on the recent identification of the mutation "leader" of this tumor. If succeed provide a widely available therapeutic alternative compared with current cancer therapies, with low toxicity. In addition it would open a new line of research with CYP17 enzyme inhibitors that could alter the course and outcome, usually fatal, in advanced stages of disease.

NCT01584297

Conditions

1. Granulosa Cell Tumour of the Ovary

Interventions

1. Drug: Ketoconazole

MeSH:Granulosa Cell Tumor

- Availability of sufficient biopsy material to confirm the diagnosis by a centralized pathologist and determination of the FOXL2 402C mutation → G (C134W). - Metastatic or unresectable disease. --- C134W ---

Granulosa Cell ovarian carcinoma is an infrequent subtype of neoplasia well differentiated from epithelial tumors. They account for 5% of all ovarian malignancies and, with an incidence of 0.4-1.2 cases per 100000 habitants, is considered as a rare disease. Though most cases are identified at initial stages and can be cured through surgical resection, distant recurrences have been documented even 10 years after resecting the primary tumor. At advanced stage it is a lethal disease. Unfortunately because of the low incidence of this disease randomized clinical trials are lacking. In fact current evidence for treatment is provided by case reports, retrospective studies and phase II clinical trials performed one decade ago. Orteronel, a novel, orally active, selective inhibitor of 17,20-lyase, is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostate cancer and breast cancer. Orteronel is expected to suppress sex hormone levels in both circulation and relevant hormone-dependent malignant tissue. Since sex hormone overproduction has been demonstrated in granulosa cell ovarian tumors and seems to play a major role in this disease, this study will assess the efficacy or orteronel treating such tumors.

NCT02101684

Conditions

1. Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors

Interventions

1. Drug: Orteronel 300mg BID

MeSH:Ovarian Neoplasms

HPO:Ovarian neoplasm

- Availability of sufficient biopsy material to confirm the malignant diagnosis of granulosa cell ovarian tumor by a centralized pathologist and to perform the determine the FOXL2 402C mutation → G (C134W). --- C134W ---

The good tolerability profile of enzalutamide, the fact that the administration of steroids is not necessary and the impressive results achieved in prostate cancer, make this drug an ideal candidate to be tested in ovarian granulosa cancer, a tumor that could somehow be considered as "female prostate cancer".

NCT03464201

Conditions

1. Ovarian Cancer

Interventions

1. Drug: Enzalutamide 40 MG

MeSH:Ovarian Neoplasms

HPO:Ovarian neoplasm

Inclusion Criteria: - Patients who have given written informed consent - Women aged 18 years or over - Eastern Cooperative Oncology Group (ECOG) ≤ 1 - Diagnosis of histologically confirmed ovarian granulose carcinoma - Availability of sufficient biopsy material for confirmation of the diagnosis by a centralized pathologist and determination of the mutation FOXL2402C→ G(C134W). --- C134W ---