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

NCT01584297 | Terminated Phase 2

• 2 other identifiers: GETHI 2011-032012-001948-21
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 10

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

Keywords

Granulosa Cell Tumour

Outcome Measures

Primary Outcomes (1)

• 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

  Every 8 weeks

Secondary Outcomes (5)

• Clinical benefit

  Every 8 weeks

• Progression-free survival

  Every 8 weeks

• Overall survival

  Untill death

• Quality of life

  Every 4 weeks

• Safety profile

  Every 4 weeks

Study Arms (1)

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.

Drug: Ketoconazole

Interventions

Ketoconazole 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.

Also known as: Fungarest

Ketoconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grupo Español de Tumores Huérfanos e Infrecuentes: lead

Study Sites (10)

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

Location

Hospital Reina Sofía

Córdoba, Cordoba, 14004, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Hospital La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Morales Meseguer

Murcia, Murcia, 30008, Spain

Location

Complejo Hospitalario de Navarra

Navarra, Navarre, 31008, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Palma de Mallorca, 07198, Spain

Location

Hospital Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

Location

Related Publications (1)

• 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.

  PMID: 36708371 DERIVED

MeSH Terms

Conditions

Granulosa Cell Tumor

Interventions

Ketoconazole

Condition Hierarchy (Ancestors)

Sex Cord-Gonadal Stromal Tumors; Neoplasms, Gonadal Tissue; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jesus Garcia-Donas, MD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2012
• First Posted: April 24, 2012
• Study Start: October 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: January 21, 2015

Record last verified: 2015-01

Locations

ES (10)