Clinical trial NCT00910091: The Study of Oral Steroid Sulphatase Inhibitor BN83495 Versus Megestrol Acetate (MA) in Women With Advanced or Recurrent Endometrial Cancer
Official title: A Phase II International Multicentre Randomised Open Label Study of Oral Steroid Sulphatase Inhibitor BN83495 Versus Megestrol Acetate (MA) in Women With Advanced or Recurrent Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Endometrial cancer
Antitumour efficacy in women with advanced endometrial cancer
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2009-05-29
Enrollment: 73
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will explore the safety and efficacy of BN83485 compared to Megestrol Acetate (MA) on progression free survival (PFS) in post menopausal patients with endometrial cancer.

Detailed description: The Primary Objective in this study is to determine the antitumour efficacy of BN83495 measured by the percentage of women with advanced or recurrent endometrial cancer who have neither progressed nor died after 6 months of treatment.

Eligibility criteria: Inclusion Criteria:

* Provision of written informed consent prior to any study related procedures
* Post-menopausal or ovariectomised female patients over the age of 18 years with advanced or recurrent endometrial carcinoma
* Histologically confirmed diagnosis endometrial carcinoma (primary tumour or metastasis)
* Not eligible for surgery or radiotherapy alone, at Investigator's discretion
* Documented Estrogen Receptor (ER) positivity in the primary tumour or in the metastatic tissue if the primary tumour is unavailable (ER positivity is defined by at least 10% positive cells)
* No other history of malignant disease except treated basal cell or in situ cervical carcinoma in the previous 5 years. In case of previous malignant disease, pathological confirmation of metastatic endometrial cancer will be done at Investigator's discretion
* Eastern Cooperative Oncology Group (ECOG) Performance status ≤2
* At least one measurable disease site

  * minimum indicator lesion size: 20 mm (conventional techniques) or 10 mm (spiral CT scan)
  * target lesions not situated in irradiated area
* Life expectancy ≥6 months
* Adequate organ function as defined by the following criteria:

  * Haemoglobin ≥10 g/dL
  * Absolute neutrophil count (ANC) ≥1500/μL
  * Platelets ≥100,000/μL
  * Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50 ml/min
  * Serum AST and serum ALT ≤2.5x ULN or AST and ALT ≤5x ULN if liver metastases
  * Total serum bilirubin ≤1.5x ULN
  * Serum albumin ≥3.0 g/dL
  * Cardiac function ≤New York Heart Association (NYHA) class II
* Patients must have recovered from surgery, radiotherapy and toxicities of adjuvant chemotherapy treatment if applicable
* Patients must be willing and able to participate in a clinical trial (including the completion of all necessary study procedures)
* Patients must be able to swallow oral medication

Exclusion Criteria:

* Use of any investigational agent in the 4 weeks prior to enrollment in this study
* Prior systemic treatment for endometrial cancer (including hormonal treatment, chemotherapy, antiangiogenic or targeted therapies)with the exception of chemotherapy in the adjuvant setting, having been completed at least 6 months prior to randomisation
* Known central nervous system (CNS) metastases
* Ongoing cardiac dysrhythmias of National Cancer Institute Common Toxicity Criteria Adverse Events (NCI CTC AE) grade ≥2, atrial fibrillation of any grade, QTcF interval \>460 msec.
* Patients with contraindications to Megestrol Acetate (MA) including hypersensitivity to one of the drug product, any active arterial or venous thromboembolic event and/or uncontrolled hypertension. Patients receiving anticoagulation for a prior thromboembolic event may be enrolled in the study at the Investigator's discretion
* Concomitant use of carbonic anhydrase II inhibitors (e.g. acetazolamide, dichlorphenamide, methazolamide)
* History of hypersensitivity to BN83495 or drugs with a similar chemical structure
* Likely to require treatment during the study with drugs that are not permitted by the study protocol
* Abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study

Primary outcomes:
measure: Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died
timeFrame: Up to 6 months
Secondary outcomes:
measure: Percentage of Participants With Adverse Event (AE)
timeFrame: Up to Day 28 follow-up
measure: Tolerability of BN83495 Based on Length of Exposure
timeFrame: Up to 2 years
measure: Tolerability of BN83495 Based on Cumulative Dose Administered
timeFrame: Up to 2 years
measure: Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions
timeFrame: Up to 2 years
measure: Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score
timeFrame: Up to week 32
measure: Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks
timeFrame: Up to 2 years
measure: Percentage of Participants With Overall Response (OR) Including CR and PR
timeFrame: Up to 2 years
measure: Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation
timeFrame: Up to 2 years
measure: Duration of Response (DR) in Responders
timeFrame: At 2 years
measure: Overall Survival (OS)
timeFrame: At 2 years
measure: Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwzickenhuis-Campus Aalst
city: Bruxelles
country: Belgium
facility: Centre Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
city: Wilrijk
country: Belgium
facility: Sint Augustinus
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha
country: Czechia
facility: Gynekologicko-porodnicka klinika
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni s.r.o. - Masarykova nemocnice Usti nad Labem
city: Besançon
country: France
facility: Hôpital Jean Minjoz
city: BORDEAUX cedex
country: France
facility: Institut Bergonié
city: CAEN cedex 05
country: France
facility: Centre François Baclesse
city: LILLE cedex
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: MARSEILLE cedex 9
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Institut Curie
city: POITIERS cedex
country: France
facility: CHU Poitiers
city: REIMS cedex
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: CHU Reims
city: Rennes
country: France
facility: Centre Eugène Marquis
city: ROUEN cedex 1
country: France
facility: Centre Henri Becquerel
city: SAINT-HERBLAIN cedex
country: France
facility: Centre René Gauducheau
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Miskolc
country: Hungary
facility: BAZ Megyei Kórház és Egyetemi Oktató Kórház, Sugártherápiás és Onkológiai Intézet
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Orvos-és Gyógyszerésztudományi Centrum
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Liepaja
country: Latvia
facility: Piejuras Hospital, Oncologic Clinic
city: Riga
country: Latvia
facility: Riga Eastern CUH - Latvian Oncology Centre, Department No 9
city: Kaunas
country: Lithuania
facility: Kauno universiteto medicinos kliniku onkologijos ligonine
city: Vilnius
country: Lithuania
facility: Vilniaus universiteto Onkologijos institutas
city: Chisinau
country: Moldova, Republic of
facility: Institutul Oncologic
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej
city: Poznan
country: Poland
facility: Uniwersytet Medyczny
city: Poznan
country: Poland
facility: Oddział Ginekologii Onkologicznej Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Poznaniu
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut Marii Sklodowskiej Curie
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology Dispensary
city: Obninsk
country: Russian Federation
facility: Medical Radiology Research Center of RAMS
city: Orenburg
country: Russian Federation
facility: GUZ "Orenburg Regional Clinical Oncology Dispensary"
city: Perm
country: Russian Federation
facility: Perm Regional Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: GUZ of Stavropol Territorial Clinical Oncological Dispensary, Pyatigorsk Branch
city: Saint Petersburg
country: Russian Federation
facility: FGU "Research Institute of Oncology named after N.N.Petrov"
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg GUZ City Clinical Oncology Dispensary
city: Tomsk
country: Russian Federation
facility: OOO "Sibmedcenter"
city: Barcelona
country: Spain
facility: H. Universitario Vall d´Hebron
city: Madrid
country: Spain
facility: H. Universitario 12 de Octubre
city: Oviedo
country: Spain
facility: H. Universitario Central de Asturias
city: San Carlos
country: Spain
facility: H. Clinico Universitario San Carlos
city: Chernivtsi
country: Ukraine
facility: Oblasnyi onkologichnyi klinichnyi dyspanser, misto Uzhgorod. Uzhgorods'kyi natsionalnyi universytet
city: Kharkiv
country: Ukraine
facility: DU "Instytut medychnoi radiologii im. S.P. Grygorieva AMN Ukrainy"
city: Kyiv
country: Ukraine
facility: DU "Natsionalnyi instytut raku", m. Kyiv
city: Lviv
country: Ukraine
facility: Lvivskyi derzhavnyi onkologichnyi regionalnyi likuvalno-diagnostychnyi tsentr
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre, Gartnavel General Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester, Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: University of Liverpool Clatterbridge Centre for Oncology
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: