Granulosa Cell Tumour of the OvaryPhase 2GreKoNCT01584297
Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary
A Phase 2 study testing Ketoconazole in people with Granulosa Cell Tumour of the Ovary, run by Grupo Español de Tumores Huérfanos e Infrecuentes at 10 sites in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Granulosa Cell Tumour of the Ovary
- What is being tested?
- Ketoconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 10 sitesSpain
- Study dates
- Oct 2012to Nov 2014
- 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
- Patients obtained their written informed consent.
- Women ≥18 years old.
- ECOG ≤ 1.
- Histologically confirmed carcinoma of granulosa cell in ovary.
- 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.
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- Imaging measurable disease.
- Life expectancy ≥ 12 weeks.
- Patients with adequate hepatic function, defined by:
- Serum values of AST and ALT ≤ 3 x UNL (except in the presence of metastases then allowed values ≤ 5 x UNL)
- Total bilirubin ≤ 1.5 x UNL
- Patients with adequate bone marrow function, defined by:
- Absolute neutrophil count ≥ 1.5 x 10*9 / L
- Platelets ≥ 100 x 10*9 / L
- Hb > 9 g / dL
- Patients with adequate renal function: serum creatinine ≤ 1.5 x UNL.
- Absence of any impediment to comply with the study protocol.
- Women of childbearing potential, sexually active, not under hysterectomy or bilateral adnexectomy, should follow the following guidelines on contraception:
- Negative serum or urine pregnancy test within 72 hours before the start of treatment.
- Use of a medically accepted contraceptive method during: the 2 months prior to study treatment, during the study and 3 months after the last dose of study treatment.
Who cannot join
- Patients with another primary tumor 2 years before starting the study drug, with the exception of cervical carcinoma in situ or adequately treated or removed completely or basalioma or superficial bladder carcinoma.
- 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.
- Patients with heart failure or clinically significant heart disease, including any of the following:
- History or presence of uncontrolled severe ventricular arrhythmia.
- Clinically significant bradycardia at rest.
- LVEF <45% assessed by 2-D echocardiogram (ECHO) or MUGA.
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- Any of the following diseases within 6 months prior to the start of study drug: Myocardial infarction (MI), severe or unstable angina, coronary revascularization, congestive heart failure (CHF), stroke (CVA), transient ischemic attack (TIA).
- Patients with gastrointestinal function failure or gastric disease that significantly alter the ketoconazole absorption, for example, severe ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption, extensive resection (> 1m) of the small intestine or inability to swallow oral medication. The partial or total gastrectomy is not an exclusion criteria.
- Diagnosis of infection with human immunodeficiency virus (HIV).
- Pregnant women or nursing.
- Women of childbearing potential not using effective contraceptive method.
- Patients who are unwilling or unable to comply with the protocol.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites
Hospital Universitario Fundación Alcorcón
Alcorcón, Madrid, 28922
Hospital del Mar
Barcelona, Barcelona, 08003
Hospital Reina Sofía
Córdoba, Cordoba, 14004
Hospital La Paz
Madrid, Madrid, 28046
Hospital Morales Meseguer
Murcia, Murcia, 30008
Complejo Hospitalario de Navarra
Navarra, Navarre, 31008
Hospital Central de Asturias
Oviedo, Principality of Asturias, 33006
Hospital Son Llatzer
Palma de Mallorca, Palma de Mallorca, 07198
Complejo Hospitalario Universitario de Santiago de Compostela
Santiago de Compostela, A Coruña, 15706
Hospital Universitario y Politécnico La Fe
Valencia, Valencia, 46026
About this study
Official title: Open Phase II Study of Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary. GreKo Study.
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.
- Conditions
- Granulosa Cell Tumour of the Ovary
- Being tested
- Ketoconazole
- Keywords
- Granulosa Cell Tumour
- Medical subject headings
- Granulosa Cell Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetoconazoleDrug
Also called Fungarest
Patients will receive ketoconazole, 400 mg three times a day. Study treatment period will be during 6 months or up to progression disease, unacceptable toxicity, death or withdraw from the study for any reason.
| Study group | Role | What they receive |
|---|---|---|
| Ketoconazole | Experimental | Patients will receive ketoconazole, 400 mg three times a day. Study treatment period will be during 6 months or up to progression disease, unacceptable toxicity, death or withdraw from the study for any reason. Receives: Drug: Ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
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 evaluator
Measured: Every 8 weeks
Secondary outcomes (5)
Clinical benefit
Clinical benefit defined as stable disease for more than 6 months plus complete and partial response rates, measured by an external evaluator.
Measured: Every 8 weeks
Progression-free survival
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.
Measured: Every 8 weeks
Overall survival
Overall survival, defined as the time since the start of treatment until the patient dies by any cause.
Measured: Untill death
Quality of life
Quality of life measured by the validated in Spanish EORTC QLQ-C30 questionnaire.
Measured: Every 4 weeks
Safety profile
Toxicities will be classified according to the NCI-CTCAE v4.03
Measured: Every 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2012 (estimated)
- Study startOct 2012
- Primary completionNov 2014
- Study completionNov 2014
Why it stopped: Insufficient 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 Granulosa Cell Tumour of the OvaryStudies 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español de Tumores Huérfanos e Infrecuentes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jesus Garcia-Donas, MD, Study director, Hospital Universitario Fundación de Alcorcón, Servicio de Oncología Médica, c/ Budapest, 1,28922 Alcorcón (Madrid), Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01584297
- Sponsor's protocol ID
- GETHI 2011-03
- Other IDs
- 2012-001948-21
- Acronym
- GreKo
- Status last verified
- Jan 2015
- First submitted
- 22 Apr 2012
- Last updated
- 21 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Garcia-Donas J, Hurtado A, Garrigos L, Santaballa A, Redondo A, Vidal L, Lainez N, Guerra E, Rodriguez V, Cueva J, Bover I, Palacio I, Rubio MJ, Prieto M, Lopez-Guerrero JA, Rodriguez-Moreno JF, Garcia-Casado Z, Garcia-Martinez E, Taus A, de Castro IP, Navarro P, Grande E; Spanish Group for Research in Orphan, Infrequent Tumors (GETHI). Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03. Clin Transl Oncol. 2023 Jul;25(7):2090-2098. doi: 10.1007/s12094-023-03085-w. Epub 2023 Jan 28.
PubMed 36708371
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Phase II Study of Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary. GreKo Study.
- ClinicalTrials.gov ID
- NCT01584297
- Acronym / sponsor ID
- GreKo / GETHI 2011-03
- Conditions
- Granulosa Cell Tumour of the Ovary
- Keywords
- Granulosa Cell Tumour
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient recruitment rate
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Grupo Español de Tumores Huérfanos e InfrecuentesUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 24 Apr 2012 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketoconazole | Experimental | Drug: KetoconazolePatients will receive ketoconazole, 400 mg three times a day. Study treatment period will be during 6 months or up to progression disease, unacceptable toxicity, death or withdraw from the study for any reason. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients obtained their written informed consent.
- Women ≥18 years old.
- ECOG ≤ 1.
- Histologically confirmed carcinoma of granulosa cell in ovary.
- Availability of sufficient biopsy material to confirm the diagnosis by a centralized pathologist and determination of the FOXL2 402C mutation → G (C134W).
Key exclusion criteria (12 listed)
- Patients with another primary tumor 2 years before starting the study drug, with the exception of cervical carcinoma in situ or adequately treated or removed completely or basalioma or superficial bladder carcinoma.
- 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.
- Patients with heart failure or clinically significant heart disease, including any of the following:
- History or presence of uncontrolled severe ventricular arrhythmia.
- Clinically significant bradycardia at rest.
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 |
|---|---|---|
| KetoconazoleAlso: FungarestPatients will receive ketoconazole, 400 mg three times a day. Study treatment period will be during 6 months or up to progression disease, unacceptable toxicity, death or withdraw from the study for any reason. | Drug | Ketoconazole |
Primary outcome
Overall response rate
Time frame: Every 8 weeks
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 evaluator
5 secondary outcomes
Clinical benefit
Time frame: Every 8 weeks
Progression-free survival
Time frame: Every 8 weeks
Overall survival
Time frame: Untill death
Quality of life
Time frame: Every 4 weeks
Safety profile
Time frame: Every 4 weeks
Results and safety
The study was stopped early (reason given: Insufficient recruitment rate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2015.
- Derived from this study: PubMed 36708371Garcia-Donas J, Hurtado A, Garrigos L, Santaballa A, Redondo A, Vidal L, Lainez N, Guerra E, Rodriguez V, Cueva J, Bover I, Palacio I, Rubio MJ, Prieto M, Lopez-Guerrero JA, Rodriguez-Moreno JF, Garcia-Casado Z, Garcia-Martinez E, Taus A, de Castro IP, Navarro P, Grande E; Spanish Group for Research in Orphan, Infrequent Tumors (GETHI). Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03. Clin Transl Oncol. 2023 Jul;25(7):2090-2098. doi: 10.1007/s12094-023-03085-w. Epub 2023 Jan 28.
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.
Jesus Garcia-Donas, MD study director
Hospital Universitario Fundación de Alcorcón, Servicio de Oncología Médica, c/ Budapest, 1,28922 Alcorcón (Madrid), Spain
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketoconazole in people with Granulosa Cell Tumour of the Ovary, run by Grupo Español de Tumores Huérfanos e Infrecuentes at 10 sites in Spain.
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 20 inclusion and 12 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 21 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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: Insufficient 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?
Overall response rate (time frame: Every 8 weeks). 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 NCT01584297, 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 21 Jan 2015.