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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Grupo Español de Tumores Huérfanos e Infrecuentes
Sponsor:
Information provided by (Responsible Party):
Grupo Español de Tumores Huérfanos e Infrecuentes
ClinicalTrials.gov Identifier:
NCT01584297
First received: April 22, 2012
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Granulosa Cell Tumour of the Ovary
Drug: Ketoconazole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Grupo Español de Tumores Huérfanos e Infrecuentes:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Clinical benefit [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Clinical benefit defined as stable disease for more than 6 months plus complete and partial response rates, measured by an external evaluator.

  • Progression-free survival [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Overall survival [ Time Frame: Untill death ] [ Designated as safety issue: No ]
    Overall survival, defined as the time since the start of treatment until the patient dies by any cause.

  • Quality of life [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
    Quality of life measured by the validated in Spanish EORTC QLQ-C30 questionnaire.

  • Safety profile [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
    Toxicities will be classified according to the NCI-CTCAE v4.03


Estimated Enrollment: 17
Study Start Date: October 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Name: Fungarest

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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).
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01584297

Contacts
Contact: Juan L Sanz +34918166804 juanluis.sanz@apices.es
Contact: Ana M Moreno +34918166804 ext 100 ana.moreno@apices.es

Locations
Spain
Complejo Hospitalario Universitario de Santiago de Compostela Recruiting
Santiago de Compostela, A Coruña, Spain, 15706
Contact: Juan F Cueva, MD    +34 988385471    juancueva@telefonica.net   
Principal Investigator: Juan F Cueva, MD         
Hospital Central de Asturias Recruiting
Oviedo, Asturias, Spain, 33006
Contact: Emilio García Esteban, MD    +34 985108000    eestebang@seom.org   
Principal Investigator: Emilio Garcia Esteban, MD         
Hospital Universitario Fundación Alcorcón Recruiting
Alcorcón, Madrid, Spain, 28922
Contact: Alicia Hurtado, MD    +34 666383649    ahurtado@fhalcorcon.es   
Principal Investigator: Alicia Hurtado, MD         
Hospital del Mar Recruiting
Barcelona, Spain, 08003
Contact: Laia Garrigos, MD    +34 93 248 30 00    LGarrigos@parcdesalutmar.cat   
Principal Investigator: Laia Garrigos, MD         
Hospital Reina Sofía Recruiting
Cordoba, Spain, 14004
Contact: Maria J Rubio, MD    +34 957 010 000    mjruper@hotmail.com   
Principal Investigator: Maria J Rubio, MD         
Hospital La Paz Recruiting
Madrid, Spain, 28046
Contact: Andrés Redondo, MD    +34 917277000 ext 41138    aredondo12@gmail.com   
Principal Investigator: Andres Redondo, MD         
Hospital Morales Meseguer Recruiting
Murcia, Spain, 30008
Contact: Elena García, MD    +34 96836520    helenagarciam@gmail.com   
Principal Investigator: Elena García, MD         
Complejo Hospitalario de Navarra Recruiting
Navarra, Spain, 31008
Contact: Nuria Lainez, MD         
Principal Investigator: Nuria Lainez, MD         
Hospital Son Llatzer Recruiting
Palma de Mallorca, Spain, 07198
Contact: Isabel Bover, MD    871202184    ibover@hsll.es   
Principal Investigator: Isabel Bover, MD         
Hospital Universitario y Politécnico La Fe Recruiting
Valencia, Spain, 46026
Contact: Ana Santaballa, MD    +34 966616487    santaballa_ana@gva.es   
Principal Investigator: Ana Santaballa, MD         
Sponsors and Collaborators
Grupo Español de Tumores Huérfanos e Infrecuentes
Investigators
Study Director: Jesus Garcia-Donas, MD Hospital Universitario Fundación de Alcorcón, Servicio de Oncología Médica, c/ Budapest, 1,28922 Alcorcón (Madrid), Spain
  More Information

No publications provided

Responsible Party: Grupo Español de Tumores Huérfanos e Infrecuentes
ClinicalTrials.gov Identifier: NCT01584297     History of Changes
Other Study ID Numbers: GETHI 2011-03, 2012-001948-21
Study First Received: April 22, 2012
Last Updated: February 15, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Grupo Español de Tumores Huérfanos e Infrecuentes:
Granulosa Cell Tumour

Additional relevant MeSH terms:
Neoplasms
Ovarian Neoplasms
Granulosa Cell Tumor
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Sex Cord-Gonadal Stromal Tumors
Neoplasms, Gonadal Tissue
Neoplasms by Histologic Type
Ketoconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014