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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Grupo Español de Tumores Huérfanos e Infrecuentes
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Grupo Español de Tumores Huérfanos e Infrecuentes
ClinicalTrials.gov Identifier:
NCT02101684
First received: March 26, 2014
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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.

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.


Condition Intervention Phase
Metastatic or Advanced Non-resectable Granulosa Cell Ovarian Tumors
Drug: Orteronel 300mg BID
Phase 2

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Clinical benefit at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: Every 8 weeks, during 6 months ] [ Designated as safety issue: No ]
    Overall Response Rate according to RECIST 1.1 criteria.

  • Progression free survival [ Time Frame: Every 8 weeks, during 6 months ] [ Designated as safety issue: No ]
    Progression Free Survival defined as the time from the administration of the first dose of treatment to disease progression or death from any cause.

  • Overall Survival [ Time Frame: Every 12 weeks, untill death ] [ Designated as safety issue: No ]
    Overall Survival defined as the time from first dose of treatment to patient death from any cause

  • Reduction of sex hormones production. [ Time Frame: Every 8 weeks, during 6 months ] [ Designated as safety issue: No ]
    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.

  • Toxicity profile [ Time Frame: Every 4 weeks, untill end of treatment (6 months estimated) ] [ Designated as safety issue: Yes ]
    Frequency of each adverse event per patient


Estimated Enrollment: 20
Study Start Date: June 2014
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Orteronel 300mg b.i.d.
Orteronel 300mg BID (600mg per day) will be administered to all included patients in a 28 days cycle schedule.
Drug: Orteronel 300mg BID

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    1. Agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or
    2. Agree to completely abstain from intercourse.
  • 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.
  • 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.

Exclusion Criteria:

  • 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:

    1. Q-wave infarction, unless identified 6 or more months prior to screening
    2. 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.
  • 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.
  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: NCT02101684

Contacts
Contact: Jesús García-Donas, MD (+34) 917567890 jgarciadonas@gmail.com

Locations
Spain
Hospital Son Llatzer Recruiting
Palma de Mallorca, Islas Baleares, Spain, 07198
Contact: Isabel Bover, MD    +34 871202000 ext 1143    ibover@hsll.es   
Principal Investigator: Isabel Bover, MD         
Complexo Hospitalario Universitario de Santiago Recruiting
Santiago de Compostela, La Coruña, Spain, 15706
Contact: Juan Cueva, MD    +34 981951457    juancueva@telefonica.net   
Principal Investigator: Juan Cueva, MD         
Hospital Universitario Fundación Alcorcón Recruiting
Alcorcón, Madrid, Spain, 28922
Contact: Alicia Hurtado, MD    +34 916219490    ahurtado@fhalcorcon.es   
Principal Investigator: Alicia Hurtado, MD         
Complejo Hospitalario de Navarra Recruiting
Pamplona/Iruña, Navarra, Spain, 31008
Contact: Nuria Lainez, MD    +34 848422576    nuria.lainez.milagro@cfnavarra.es   
Principal Investigator: Nuria Lainez, MD         
Hospital Del Mar Recruiting
Barcelona, Spain, 08003
Contact: Laia Garrigos, MD    +34 932483137    asaao@parcdesalutmar.cat   
Principal Investigator: Laia Garrigos, MD         
Complejo Hospitalario Regional Reina Sofía Recruiting
Córdoba, Spain, 14004
Contact: María Jesús Rubio, MD    +34 957011420    mjruper@hotmail.com   
Principal Investigator: María Jesús Rubio, MD         
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Andrés Redondo, MD    +34 917277516    aredondo12@gmail.com   
Principal Investigator: Andrés Redondo, MD         
Hospital Universitario Madrid Sanchinarro Not yet recruiting
Madrid, Spain, 28050
Contact: Jesús García-Donas, MD    +34 917567890    jgarciadonas@gmail.com   
Principal Investigator: Jesús García-Donas, MD         
Hospital Universitari I Politècnic La Fe Recruiting
Valencia, Spain, 46026
Contact: Ana Santaballa, MD    +34 616477116    santaballa_ana@gva.es   
Principal Investigator: Ana Santaballa, MD         
Sponsors and Collaborators
Grupo Español de Tumores Huérfanos e Infrecuentes
Takeda
Investigators
Study Director: Jesús García-Donas, MD Hospital Universitario Madrid Sanchinarro
Principal Investigator: Alicia Hurtado, MD Hospital Universitario Fundación Alcorcón
Principal Investigator: Juan Cueva, MD COMPLEXO HOSPITALARIO UNIVERSITARIO DE SANTIAGO
Principal Investigator: Laia Garrigos, MD Hospital del Mar
Principal Investigator: María Jesús Rubio, MD COMPLEJO HOSPITALARIO REGIONAL REINA SOFÍA
Principal Investigator: Andrés Redondo, MD Hospital Universitario La Paz
Principal Investigator: Isabel Bover, MD Hospital Son Llatzer
Principal Investigator: Nuria Lainez, MD COMPLEJO HOSPITALARIO DE NAVARRA
Principal Investigator: Ana Santaballa, MD HOSPITAL UNIVERSITARI I POLITÈCNIC LA FE
  More Information

No publications provided

Responsible Party: Grupo Español de Tumores Huérfanos e Infrecuentes
ClinicalTrials.gov Identifier: NCT02101684     History of Changes
Other Study ID Numbers: GETHI 2013-01, 2013-003128-35
Study First Received: March 26, 2014
Last Updated: August 18, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

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

Additional relevant MeSH terms:
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Adnexal Diseases
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders

ClinicalTrials.gov processed this record on November 27, 2014