Ketoconazole as Inhibitor of the Enzyme CYP17 in Locally Advanced or Disseminated Granulosa Cell Tumour of Ovary

NCT ID: NCT01584297

Last Updated: 2015-01-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-11-30

Brief 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. 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

Study Design

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

Study Groups

Ketoconazole

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.

Group Type: EXPERIMENTAL

Ketoconazole

Intervention Type: DRUG

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.

Interventions

Ketoconazole

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.

Intervention Type: DRUG

Other Intervention Names

Fungarest

Eligibility Criteria

Inclusion Criteria

• 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.
• 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.

Exclusion Criteria

• 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.
• 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).
• 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.

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

Sponsors

Grupo Español de Tumores Huérfanos e Infrecuentes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesus Garcia-Donas, MD

Role: STUDY_DIRECTOR

Hospital Universitario Fundación de Alcorcón, Servicio de Oncología Médica, c/ Budapest, 1,28922 Alcorcón (Madrid), Spain

Locations

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Hospital del Mar

Barcelona, Barcelona, Spain

Hospital Reina Sofía

Córdoba, Cordoba, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Hospital La Paz

Madrid, Madrid, Spain

Hospital Morales Meseguer

Murcia, Murcia, Spain

Complejo Hospitalario de Navarra

Navarra, Navarre, Spain

Hospital Son Llatzer

Palma de Mallorca, Palma de Mallorca, Spain

Hospital Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 36708371 (View on PubMed)

Other Identifiers

2012-001948-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GETHI 2011-03

Identifier Type: -

Identifier Source: org_study_id