Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.

NCT ID: NCT02101684

Last Updated: 2018-03-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2017-01-11

Brief Summary

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.

Conditions

Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Orteronel 300mg b.i.d.

Orteronel 300mg BID (600mg per day) will be administered to all included patients in a 28 days cycle schedule.

Group Type: EXPERIMENTAL

Orteronel 300mg BID

Intervention Type: DRUG

Interventions

Orteronel 300mg BID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Voluntary written informed consent.
• Patients, even if surgically sterilized who:

1. Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or

2. 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 <=2.5 X ULN.
• Total bilirubin <=1.5 X ULN.
• Estimated creatinine clearance using the Cockcroft-Gault formula 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 metastatic disease, measurable 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
• Screening calculated ejection fraction of greater than or equal to normal by multiple gated acquisition (MUGA) scan, or by echocardiogram (ECHO).
• Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before first dose of study drug/randomization.

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:

1. Q-wave infarction, unless identified 6 or more months prior to screening

2. 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.
• 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 or to orteronel excipients.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Grupo Español de Tumores Huérfanos e Infrecuentes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesús García-Donas, MD

Role: STUDY_DIRECTOR

Hospital Universitario Madrid Sanchinarro

Alicia Hurtado, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Fundación Alcorcón

Juan Cueva, MD

Role: PRINCIPAL_INVESTIGATOR

COMPLEXO HOSPITALARIO UNIVERSITARIO DE SANTIAGO

Laia Garrigos, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital del Mar

María Jesús Rubio, MD

Role: PRINCIPAL_INVESTIGATOR

COMPLEJO HOSPITALARIO REGIONAL REINA SOFÍA

Andrés Redondo, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Paz

Isabel Bover, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Son Llatzer

Nuria Lainez, MD

Role: PRINCIPAL_INVESTIGATOR

Complejo Hospitalario de Navarra

Ana Santaballa, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Fe

Locations

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, La Coruña, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

Hospital Del Mar

Barcelona, , Spain

Complejo Hospitalario Regional Reina Sofía

Córdoba, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Hospital Universitari I Politècnic La Fe

Valencia, , Spain

Countries

Spain

References

Garcia-Donas J, Garrigos L, Lainez N, Santaballa A, Redondo A, Cueva JF, Rubio MJ, Prieto M, Lopez-Guerrero JA, Garcia-Casado Z, Barquin A, Grande E, Alia EG, Sevillano E, Bover I, Grazioso TP, Sanchez-Escribano R, Hurtado A, Navarro P, Rodriguez-Moreno JF. Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: the Greko II study (GETHI2013-01). Clin Transl Oncol. 2025 Jul;27(7):3223-3231. doi: 10.1007/s12094-024-03827-4. Epub 2024 Dec 30.

Reference Type: DERIVED

PMID: 39738931 (View on PubMed)

Other Identifiers

2013-003128-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETHI 2013-01

Identifier Type: -

Identifier Source: org_study_id