There are 3 clinical trials
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.
- 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 ---
Description: The primary endpoint is overall response rate, defined as the proportion of patients with response defined as complete or partial response according to RECIST CRITERIA 1.1 measured by an external evaluatorMeasure: Overall response rate Time: Every 8 weeks
Description: Clinical benefit defined as stable disease for more than 6 months plus complete and partial response rates, measured by an external evaluator.Measure: Clinical benefit Time: Every 8 weeks
Description: Progression-free survival is defined as the time since the start of treatment until progressive disease assessed (through evaluation by an external radiologist) according to RECIST 1.1, or death by any cause.Measure: Progression-free survival Time: Every 8 weeks
Description: Overall survival, defined as the time since the start of treatment until the patient dies by any cause.Measure: Overall survival Time: Untill death
Description: Quality of life measured by the validated in Spanish EORTC QLQ-C30 questionnaire.Measure: Quality of life Time: Every 4 weeks
Description: Toxicities will be classified according to the NCI-CTCAE v4.03Measure: Safety profile Time: Every 4 weeks
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.
- 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 ---
Description: Clinical benefit is defined as the average of patients with radiological response (partial or complete) plus stable disease longer than 6 months by RECIST 1.1 criteriaMeasure: Clinical benefit at 6 months Time: 6 months
Description: Overall Response Rate according to RECIST 1.1 criteria.Measure: Overall Response Rate Time: Every 8 weeks, during 6 months
Description: Progression Free Survival defined as the time from the administration of the first dose of treatment to disease progression or death from any cause.Measure: Progression free survival Time: Every 8 weeks, during 6 months
Description: Overall Survival defined as the time from first dose of treatment to patient death from any causeMeasure: Overall Survival Time: Every 12 weeks, untill death
Description: Significant reduction of sex hormones production will be considered as at least a reduction to half the basal level confirmed in one determination one month apart.Measure: Reduction of sex hormones production. Time: Every 8 weeks, during 6 months
Description: Frequency of each adverse event per patientMeasure: Toxicity profile Time: Every 4 weeks, untill end of treatment (6 months estimated)
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".
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 ---
Description: Number of responses according to RECIST 1.1 criteriaMeasure: Overall response rate (ORR) Time: Up to 6 months
Description: Stabilization of disease plus the sum of partial and complete responses according to RECIST 1.1 criteria.Measure: Clinical benefit rate Time: Up to 6 months
Description: Number of progression of the disease according to RECIST 1.1 criteria or death of the patient for any causeMeasure: Progression-free survival (PFS) Time: Up to 6 months
Description: Number of deaths for any cause.Measure: Overall survival (OS) Time: Up to 6 months
Description: Number of Adverse Events per patientMeasure: Incidence of Treatment-Emergent Adverse Events Time: Up to 6 months