Metastatic or advanced non-resectable granulosa cell ovarian tumors MedDRA version: 17.0 Level: PT Classification code 10057376 Term: Ovarian granulosa-theca cell tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Orteronel
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ORTERONEL
Current Sponsor code: TAK-700
Other descriptive name: ORTERONEL
Concentration unit: mg milligram(s)
Conce
Sponsors
Grupo Español de Tumores Huérfanos e Infrecuentes (GETHI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Voluntary written informed consent. - Patients, even if surgically sterilized who: - Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or - Agree to completely abstain from intercourse. - Patients 18 years or older. - Screening clinical laboratory values as specified below: - Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be 40 mL/minute. - Absolute neutrophil count (ANC) >=1500/mcL and platelet count >=100,000/mcL. - Histologically confirmed granulosa cell ovarian tumor with locally advanced non-resectable or metastasic disease, meseaurable or evaluable by RECIST. - 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). However study entry will be allowed based just on the histological local diagnosis. - Life expectancy >=12 weeks - ECOG PS = 2 - Ejection fraction greater or equal to the value established as normal for each center by nuclear ventriculography (VRN) or echocardiogram (ECHO). - Stability of any concurrent chronic disease (defined as absence of acute exacerbations), serious infections, or major surgery within 4 weeks before first dose of study drug/randomization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5 ;Inclusion criteria: - Voluntary written informed consent. - Patients, even if surgically sterilized who: - Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or - Agree to completely abstain from intercourse. - Patients 18 years or older. - Screening clinical laboratory values as specified below: - Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be 40 mL/minute. - Absolute neutrophil count (ANC) >=1500/mcL and platelet count >=100,000/mcL. - Histologically confirmed granulosa cell ovarian tumor with locally advanced non-resectable or metastasic disease, meseaurable or evaluable by RECIST. - 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). However study entry will be allowed based just on the histological local diagnosis. - Life expectancy >=12 weeks - ECOG PS = 2 - Ejection fraction greater or equal to the value established as normal for each center by nuclear ventriculography (VRN) or echocardiogram (ECHO). - Stability of any concurrent chronic disease (defined as absence of acute exacerbations), serious infections, or major surgery within 4 weeks before first dose of study drug/randomization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5 ;Inclusion criteria: - Voluntary written informed consent. - Patients, even if surgically sterilized who: - Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or - Agree to completely abstain from intercourse. - Patients 18 years or older. - Screening clinical laboratory values as specified below: - Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be 40 mL/minute. - Absolute neutrophil count (ANC) >=1500/mcL and platelet count >=100,000/mcL. - Histologically confirmed granulosa cell ovarian tumor with locally advanced non-resectable or metastasic disease, meseaurable or evaluable by RECIST. - 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). However study entry will be allowed based just on the histological local diagnosis. - Life expectancy >=12 weeks - ECOG PS = 2 - Ejection fraction greater or equal to the value established as normal for each center by nuclear ventriculography (VRN) or echocardiogram (ECHO). - Stability of any concurrent chronic disease (defined as absence of acute exacerbations), serious infections, or major surgery within 4 weeks before first dose of study drug/randomization. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.02)(56), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. - New York Heart Association Class III or IV heart failure. - ECG abnormalities of: - Q-wave infarction, unless identified 6 or more months prior to screening - QTc interval > 460 msec - Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ?-human chorionic gonadotropin (?-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. - Patient has received other investigational drugs within 28 days before enrollment - Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy. - Prior therapy with orteronel, ketoconazole, abiraterone, aminoglutethimide or enzalutamide. - Patients received radical radiotherapy 2 (NCI CTCAE, version 4.02)(56), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. - New York Heart Association Class III or IV heart failure. - ECG abnormalities of: - Q-wave infarction, unless identified 6 or more months prior to screening - QTc interval > 460 msec - Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ?-human chorionic gonadotropin (?-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. - Patient has received other investigational drugs within 28 days before enrollment - Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy. - Prior therapy with orteronel, ketoconazole, abiraterone, aminoglutethimide or enzalutamide. - Patients received radical radiotherapy 2 (NCI CTCAE, version 4.02)(56), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. - New York Heart Association Class III or IV heart failure. - ECG abnormalities of: - Q-wave infarction, unless identified 6 or more months prior to screening - QTc interval > 460 msec - Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ?-human chorionic gonadotropin (?-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. - Patient has received other investigational drugs within 28 days before enrollment - Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy. - Prior therapy with orteronel, ketoconazole, abiraterone, aminoglutethimide or enzalutamide. - Patients received radical radiotherapy < 4 weeks before starting the study treatment or who have not recovered from the toxicities of radiotherapy. Palliative radiotherapy of painful bone lesions is allowed up to 14 days before the start of study treatment. - Known hypersensitivity to compounds related to orteronel (abiraterone, galaterone, ketoconazole) or to orteronel excipients (mannitol, microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, magnesium aluminometasilicate, magnesium stearate, hypromellose 2910, polyethylene glycol, titanium dioxide, ferric oxide). - Uncontrolled hypertension despite appropriate medical therapy (BP of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening visit). Note: patients may be rescreened after adjustment of antihypertensive medications. - Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with participation in this study. - Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel. - Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel, including difficulty swallowing tablets.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy in terms of clinical benefit rate of orteronel in metastatic or non-resectable locally advanced granulosa cell ovarian tumors;Secondary Objective: - Assess Overall Response Rate (ORR) defined as the sum of patients who achieve a partial or complete response by RECIST 1.1 criteria. - Assess Progression Free Survival (PFS) defined as the time from the administration of the first dose of treatment to disease progression or death from any cause. - Assess Overall Survival (OS) defined as the time from first dose of treatment to patient death from any cause - Determine the impact of Orteronel in reducing sex hormone overproduction in patients, within the study population, who present hormonal overproduction at baseline - Determine the toxicity profile of Orteronel (TAK-700) in the study population;Primary end point(s): 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 criteria;Timepoint(s) of evaluation of this end point: Every 8 weeks;Main Objective: To assess the efficacy in terms of clinical benefit rate of orteronel in metastatic or non-resectable locally advanced granulosa cell ovarian tumors;Secondary Objective: - Assess Overall Response Rate (ORR) defined as the sum of patients who achieve a partial or complete response by RECIST 1.1 criteria. - Assess Progression Free Survival (PFS) defined as the time from the administration of the first dose of treatment to disease progression or death from any cause. - Assess Overall Survival (OS) defined as the time from first dose of treatment to patient death from any cause - Determine the impact of Orteronel in reducing sex hormone overproduction in patients, within the study population, who present hormonal overproduction at baseline - Determine the toxicity profile of Orteronel (TAK-700) in the study population;Primary end point(s): Clinical benefit is defined as the average | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall Response Rate according to RECIST 1.1 criteria. - Progression free survival. - Overall Survival. - Reduction of sex hormones production (serum testosterone, DHEA-S, androstenedione, progesterone and estradiol).;Timepoint(s) of evaluation of this end point: - Every 8 weeks - Every 8 weeks - Every 12 weeks - Every 8 weeks;Secondary end point(s): - Overall Response Rate according to RECIST 1.1 criteria. - Progression free survival. - Overall Survival. - Reduction of sex hormones production (serum testosterone, DHEA-S, androstenedione, progesterone and estradiol).;Timepoint(s) of evaluation of this end point: - Every 8 weeks - Every 8 weeks - Every 12 weeks - Every 8 weeks;Secondary end point(s): - Overall Response Rate according to RECIST 1.1 criteria. - Progression free survival. - Overall Survival. - Reduction of sex hormones production (serum testosterone, DHEA-S, androstenedione, progesterone and estradiol).;Timepoint(s) of evaluation of this end point: - Every 8 weeks - Every 8 weeks - Every 12 weeks - Every 8 weeks | — |
Countries
Spain
Contacts
Public ContactClinical Operatios Department;Clinical Operatios Department;Clinical Operatios Department ;;
APICES SOLUCIONES, S.L.;APICES SOLUCIONES, S.L.;APICES SOLUCIONES, S.L.
Outcome results
None listed