Metastatic or Advanced Non-resectable Granulosa Cell Ovarian TumorsPhase 2Greko IINCT02101684

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

A Phase 2 study testing Orteronel 300mg BID in people with Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors, run by Grupo Español de Tumores Huérfanos e Infrecuentes at 9 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors
What is being tested?: Orteronel 300mg BID
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 9 sitesSpain
Study dates: Jun 2014to 11 Jan 2017
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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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.

Who cannot join

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.

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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.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

Spain9 sites

Hospital Universitario Fundación Alcorcón
Alcorcón, Madrid, 28922
Hospital Del Mar
Barcelona, 08003
Complejo Hospitalario Regional Reina Sofía
Córdoba, 14004
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Madrid Sanchinarro
Madrid, 28050
Hospital Son Llatzer
Palma de Mallorca, Balearic Islands, 07198
Complejo Hospitalario de Navarra
Pamplona, Navarre, 31008
Complexo Hospitalario Universitario de Santiago
Santiago de Compostela, La Coruña, 15706
Hospital Universitari I Politècnic La Fe
Valencia, 46026

Other trials in Spain

About this study

Official title: Open Label Phase II Clinical Trial of Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.

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
Being tested: Orteronel 300mg BID
Keywords: Orteronel, Granulosa Cell Tumour
Medical subject headings: Neoplasm Metastasis, Granulosa Cell Tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Orteronel 300mg BIDDrug

Study groups in NCT02101684
Study group	Role	What they receive
Orteronel 300mg b.i.d.	Experimental	Orteronel 300mg BID (600mg per day) will be administered to all included patients in a 28 days cycle schedule. Receives: Drug: Orteronel 300mg BID

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical benefit at 6 months
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
Measured: 6 months

Secondary outcomes (5)

Overall Response Rate
Overall Response Rate according to RECIST 1.1 criteria.
Measured: Every 8 weeks, during 6 months
Progression free survival
Progression Free Survival defined as the time from the administration of the first dose of treatment to disease progression or death from any cause.
Measured: Every 8 weeks, during 6 months
Overall Survival
Overall Survival defined as the time from first dose of treatment to patient death from any cause
Measured: Every 12 weeks, untill death
Reduction of sex hormones production.
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.
Measured: Every 8 weeks, during 6 months
Toxicity profile
Frequency of each adverse event per patient
Measured: Every 4 weeks, untill end of treatment (6 months estimated)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201411 Jan 2017

First posted2 Apr 2014 (estimated)
Study startJun 2014
Primary completion11 Jan 2017
Study completion11 Jan 2017

Why it stopped: Slow recruitment rate

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Metastatic or Advanced Non-resectable Granulosa Cell Ovarian TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02101684
Sponsor's protocol ID: GETHI 2013-01
Other IDs: 2013-003128-35
Acronym: Greko II
Status last verified: Mar 2018
First submitted: 26 Mar 2014
Last updated: 5 Mar 2018
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 39738931

Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open Label Phase II Clinical Trial of Orteronel (TAK-700) in Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors. The Greko II Study.
ClinicalTrials.gov ID: NCT02101684
Acronym / sponsor ID: Greko II / GETHI 2013-01
Conditions: Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors
Keywords: Orteronel, Granulosa Cell Tumour
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Slow recruitment rate
Enrolment: 10 participants (actual)
Lead sponsor: Grupo Español de Tumores Huérfanos e InfrecuentesUniversity, hospital or other
Collaborators: Takeda
Study start: Jun 2014
Primary completion: 11 Jan 2017 (actual)
Study completion: 11 Jan 2017 (actual)
First posted: 2 Apr 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Orteronel 300mg b.i.d.	Experimental	Drug: Orteronel 300mg BIDOrteronel 300mg BID (600mg per day) will be administered to all included patients in a 28 days cycle schedule.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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

Key exclusion criteria (15 listed)

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:
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Orteronel 300mg BID	Drug	Orteronel 300mg b.i.d.

Primary outcome

Clinical benefit at 6 months
Time frame: 6 months
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

5 secondary outcomes

Overall Response Rate
Time frame: Every 8 weeks, during 6 months
Progression free survival
Time frame: Every 8 weeks, during 6 months
Overall Survival
Time frame: Every 12 weeks, untill death
Reduction of sex hormones production.
Time frame: Every 8 weeks, during 6 months
Toxicity profile
Time frame: Every 4 weeks, untill end of treatment (6 months estimated)

Results and safety

The study was stopped early (reason given: Slow recruitment rate). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2018.
Derived from this study: PubMed 39738931Garcia-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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jesús García-Donas, MD study director

Hospital Universitario Madrid Sanchinarro

Alicia Hurtado, MD principal investigator

Hospital Universitario Fundación Alcorcón

Juan Cueva, MD principal investigator

COMPLEXO HOSPITALARIO UNIVERSITARIO DE SANTIAGO

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow recruitment rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical benefit at 6 months (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02101684, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2018.