The Study of Oral Steroid Sulphatase Inhibitor BN83495 Versus Megestrol Acetate (MA) in Women With Advanced or Recurrent Endometrial Cancer

Phase 2

Completed

Conditions: Endometrial Cancer

Interventions: Drug: Megestrol Acetate (MA)
Drug: BN83495

Registration Number: NCT00910091

Lead Sponsor: Ipsen

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 73

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B- MA - 160mg	Megestrol Acetate (MA)	After eligibility is confirmed, subjects will be randomised at baseline. The randomisation number and associated treatment for the total study will be allocated by an Interactive Voice Response System (IVRS) service
A- BN 83495- 40mg	BN83495	After eligibility is confirmed, subjects will be randomised at baseline. The randomisation number and associated treatment for the total study will be allocated by an Interactive Voice Response System (IVRS) service

Primary Outcome Measures

Name	Time	Method
Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died	Up to 6 months	Subject continuation in the study and Response Evaluation Criteria in Solid Tumours (RECIST) assessment has been based on investigator assessment and not on central review. The 6 month timepoint is defined as the treatment start date +183 days (26 weeks).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Event (AE)	Up to Day 28 follow-up	Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening/disabling and Grade 5: Death
Tolerability of BN83495 Based on Length of Exposure	Up to 2 years	Length of exposure includes interruptions.
Tolerability of BN83495 Based on Cumulative Dose Administered	Up to 2 years	Cumulative dose is the actual total dose administered.
Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions	Up to 2 years	Percentage of participants who had dose interruptions and reason for interruptions as AE, study treatment forgotten, and other reasons.
Overall Survival (OS)	At 2 years	OS is defined as the time from the date of enrollment to the date of death due to any cause.
Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause	Up to 2 years
Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score	Up to week 32	EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) is a participant answered questionnaire scoring 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks	Up to 2 years	CR: Disappearance of all known disease \& no new sites / disease related symptoms confirmed at least 12 weeks after initial documentation. Disappearance of all non-target lesions. Normalization of tumor marker level confirmed at least 12 weeks after initial documentation. PR: Minimum 30% decrease in sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 12 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above normal limits. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.
Percentage of Participants With Overall Response (OR) Including CR and PR	Up to 2 years
Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation	Up to 2 years
Duration of Response (DR) in Responders	At 2 years	DR is defined as period from the time that measurement criteria are first met for CR or PR until first date of documented Progressive Disease (PD) or death. DR was assessed in participants with a best overall response of CR or PR.

Trial Locations

Locations (54): Centre Jules Bordet
🇧🇪
Bruxelles, Belgium
Onze-Lieve-Vrouwzickenhuis-Campus Aalst
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Aalst, Belgium
Hôpital Jean Minjoz
🇫🇷
Besançon, France
Institut Curie
🇫🇷
Paris, France
Oddział Ginekologii Onkologicznej Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Poznaniu
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Poznan, Poland
Oblasnyi onkologichnyi klinichnyi dyspanser, misto Uzhgorod. Uzhgorods'kyi natsionalnyi universytet
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Chernivtsi, Ukraine
Sint Augustinus
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Wilrijk, Belgium
Medical Radiology Research Center of RAMS
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Obninsk, Russian Federation
H. Universitario Vall d´Hebron
🇪🇸
Barcelona, Spain
Krajska zdravotni s.r.o. - Masarykova nemocnice Usti nad Labem
🇨🇿
Usti nad Labem, Czechia
CHU Reims
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Reims, France
Perm Regional Oncology Dispensary
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Perm, Russian Federation
UZ Leuven - Campus Gasthuisberg
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Leuven, Belgium
Fakultni nemocnice Olomouc
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Olomouc, Czechia
CHU Poitiers
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POITIERS cedex, France
Gynekologicko-porodnicka klinika
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Praha, Czechia
H. Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Centre Léon Bérard
🇫🇷
Lyon, France
Chelyabinsk Regional Clinical Oncology Dispensary
🇷🇺
Chelyabinsk, Russian Federation
GUZ "Orenburg Regional Clinical Oncology Dispensary"
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Orenburg, Russian Federation
Saint-Petersburg GUZ City Clinical Oncology Dispensary
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Saint-Petersburg, Russian Federation
Institut Bergonié
🇫🇷
BORDEAUX cedex, France
Centre François Baclesse
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CAEN cedex 05, France
Szegedi Tudományegyetem Szent-Györgyi Albert Orvos-és Gyógyszerésztudományi Centrum
🇭🇺
Szeged, Hungary
DU "Natsionalnyi instytut raku", m. Kyiv
🇺🇦
Kyiv, Ukraine
H. Clinico Universitario San Carlos
🇪🇸
San Carlos, Spain
GUZ of Stavropol Territorial Clinical Oncological Dispensary, Pyatigorsk Branch
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Pyatigorsk, Russian Federation
Daugavpils Regional Hospital
🇱🇻
Daugavpils, Latvia
Piejuras Hospital, Oncologic Clinic
🇱🇻
Liepaja, Latvia
Vilniaus universiteto Onkologijos institutas
🇱🇹
Vilnius, Lithuania
Centre Oscar Lambret
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LILLE cedex, France
Institut Paoli Calmettes
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MARSEILLE cedex 9, France
Institut Jean Godinot
🇫🇷
REIMS cedex, France
Beatson Oncology Centre, Gartnavel General Hospital
🇬🇧
Glasgow, United Kingdom
St James's University Hospital
🇬🇧
Leeds, United Kingdom
University Hospitals of Leicester, Leicester Royal Infirmary
🇬🇧
Leicester, United Kingdom
OOO "Sibmedcenter"
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Tomsk, Russian Federation
Christie Hospital NHS Trust
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Manchester, United Kingdom
University of Liverpool Clatterbridge Centre for Oncology
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Liverpool, United Kingdom
Centre Eugène Marquis
🇫🇷
Rennes, France
Centre Henri Becquerel
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ROUEN cedex 1, France
Centre René Gauducheau
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SAINT-HERBLAIN cedex, France
BAZ Megyei Kórház és Egyetemi Oktató Kórház, Sugártherápiás és Onkológiai Intézet
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Miskolc, Hungary
Centrum Onkologii Ziemi Lubelskiej
🇵🇱
Lublin, Poland
Institut Gustave Roussy
🇫🇷
Villejuif, France
FGU "Research Institute of Oncology named after N.N.Petrov"
🇷🇺
Saint Petersburg, Russian Federation
H. Universitario Central de Asturias
🇪🇸
Oviedo, Spain
Institutul Oncologic
🇲🇩
Chisinau, Moldova, Republic of
Riga Eastern CUH - Latvian Oncology Centre, Department No 9
🇱🇻
Riga, Latvia
Kauno universiteto medicinos kliniku onkologijos ligonine
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Kaunas, Lithuania
Centrum Onkologii Instytut Marii Sklodowskiej Curie
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Warszawa, Poland
DU "Instytut medychnoi radiologii im. S.P. Grygorieva AMN Ukrainy"
🇺🇦
Kharkiv, Ukraine
Lvivskyi derzhavnyi onkologichnyi regionalnyi likuvalno-diagnostychnyi tsentr
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Lviv, Ukraine
Uniwersytet Medyczny
🇵🇱
Poznan, Poland