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

Endometrial Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910091
• Other study ID #: X-55-58064-004
• Secondary ID: 2009-010613-68
• Status: Completed
• Phase: Phase 2
• Start date: August 2009
• Est. completion date: July 2013

Study information

• Verified date: January 2019
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: July 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• BN83495
BN83495 will be administered as a 40 mg tablet once a day orally
• Megestrol Acetate (MA)
MA will be administered orally as 160mg daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

Belgium,  Czechia,  France,  Hungary,  Latvia,  Lithuania,  Moldova, Republic of,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died	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).	Up to 6 months
Secondary	Percentage of Participants With Adverse Event (AE)	Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening/disabling and Grade 5: Death	Up to Day 28 follow-up
Secondary	Tolerability of BN83495 Based on Length of Exposure	Length of exposure includes interruptions.	Up to 2 years
Secondary	Tolerability of BN83495 Based on Cumulative Dose Administered	Cumulative dose is the actual total dose administered.	Up to 2 years
Secondary	Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions	Percentage of participants who had dose interruptions and reason for interruptions as AE, study treatment forgotten, and other reasons.	Up to 2 years
Secondary	Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of =10% on the EuroQoL Score	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.	Up to week 32
Secondary	Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] =12 Weeks	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.	Up to 2 years
Secondary	Percentage of Participants With Overall Response (OR) Including CR and PR		Up to 2 years
Secondary	Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation		Up to 2 years
Secondary	Duration of Response (DR) in Responders	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.	At 2 years
Secondary	Overall Survival (OS)	OS is defined as the time from the date of enrollment to the date of death due to any cause.	At 2 years
Secondary	Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause		Up to 2 years