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

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

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.

Study Overview

• Status: Completed
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: BN83495; Drug: Megestrol Acetate (MA)

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.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Onze-Lieve-Vrouwzickenhuis-Campus Aalst
  • Bruxelles, Belgium, 1000
    • Centre Jules Bordet
  • Leuven, Belgium, 3000
    • UZ Leuven - Campus Gasthuisberg
  • Wilrijk, Belgium, 2610
    • Sint Augustinus
• Czechia
  • Olomouc, Czechia, 775 20
    • Fakultní nemocnice Olomouc
  • Praha, Czechia, 100 34
    • Gynekologicko-porodnicka klinika
  • Usti nad Labem, Czechia, 401 13
    • Krajska zdravotni s.r.o. - Masarykova nemocnice Usti nad Labem
• France
  • BORDEAUX cedex, France, 33076
    • Institut Bergonié
  • Besançon, France, 25000
    • Hôpital Jean Minjoz
  • CAEN cedex 05, France, 14076
    • Centre Francois Baclesse
  • LILLE cedex, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Leon Berard
  • MARSEILLE cedex 9, France, 13273
    • Institut Paoli Calmettes
  • POITIERS cedex, France, 86021
    • CHU Poitiers
  • Paris, France, 75005
    • Institut Curie
  • REIMS cedex, France, 51056
    • Institut Jean Godinot
  • ROUEN cedex 1, France, 76038
    • Centre Henri Becquerel
  • Reims, France, 51056
    • CHU Reims
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • SAINT-HERBLAIN cedex, France, 44805
    • Centre Rene Gauducheau
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Hungary
  • Miskolc, Hungary, H-3501
    • BAZ Megyei Kórház és Egyetemi Oktató Kórház, Sugártherápiás és Onkológiai Intézet
  • Szeged, Hungary, H-6720
    • Szegedi Tudományegyetem Szent-Györgyi Albert Orvos-és Gyógyszerésztudományi Centrum
• Latvia
  • Daugavpils, Latvia, LV-5417
    • Daugavpils Regional Hospital
  • Liepaja, Latvia, LV-3401
    • Piejuras Hospital, Oncologic Clinic
  • Riga, Latvia, LV-1079
    • Riga Eastern CUH - Latvian Oncology Centre, Department No 9
• Lithuania
  • Kaunas, Lithuania, LT-45434
    • Kauno universiteto medicinos kliniku onkologijos ligonine
  • Vilnius, Lithuania, LT-08660
    • Vilniaus universiteto Onkologijos institutas
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Institutul Oncologic
• Poland
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej
  • Poznan, Poland, 60-535
    • Uniwersytet Medyczny
  • Poznan, Poland, 61-878
    • Oddział Ginekologii Onkologicznej Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Poznaniu
  • Warszawa, Poland, 02-781
    • Centrum Onkologii Instytut Marii Sklodowskiej Curie
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Clinical Oncology Dispensary
  • Obninsk, Russian Federation, 249036
    • Medical Radiology Research Center of RAMS
  • Orenburg, Russian Federation, 460021
    • GUZ "Orenburg Regional Clinical Oncology Dispensary"
  • Perm, Russian Federation, 614066
    • Perm Regional Oncology Dispensary
  • Pyatigorsk, Russian Federation, 357502
    • GUZ of Stavropol Territorial Clinical Oncological Dispensary, Pyatigorsk Branch
  • Saint Petersburg, Russian Federation, 197758
    • FGU "Research Institute of Oncology named after N.N.Petrov"
  • Saint-Petersburg, Russian Federation, 198255
    • Saint-Petersburg GUZ City Clinical Oncology Dispensary
  • Tomsk, Russian Federation, 634041
    • OOO "Sibmedcenter"
• Spain
  • Barcelona, Spain, 08036
    • H. Universitario Vall d´Hebron
  • Madrid, Spain, 28041
    • H. Universitario 12 de octubre
  • Oviedo, Spain, 33006
    • H. Universitario Central de Asturias
  • San Carlos, Spain, 28040
    • H. Clinico Universitario San Carlos
• Ukraine
  • Chernivtsi, Ukraine, 58000
    • Oblasnyi onkologichnyi klinichnyi dyspanser, misto Uzhgorod. Uzhgorods'kyi natsionalnyi universytet
  • Kharkiv, Ukraine, 61024
    • DU "Instytut medychnoi radiologii im. S.P. Grygorieva AMN Ukrainy"
  • Kyiv, Ukraine, 03022
    • DU "Natsionalnyi instytut raku", m. Kyiv
  • Lviv, Ukraine, 79031
    • Lvivskyi derzhavnyi onkologichnyi regionalnyi likuvalno-diagnostychnyi tsentr
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson Oncology Centre, Gartnavel General Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester, Leicester Royal Infirmary
  • Liverpool, United Kingdom, CH63 4JY
    • University of Liverpool Clatterbridge Centre for Oncology
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A- BN 83495- 40mg; 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	Drug: BN83495; BN83495 will be administered as a 40 mg tablet once a day orally
Active Comparator: B- MA - 160mg; 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	Drug: Megestrol Acetate (MA); MA will be administered orally as 160mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Tolerability of BN83495 Based on Length of Exposure	Length of exposure includes interruptions.	Up to 2 years
Tolerability of BN83495 Based on Cumulative Dose Administered	Cumulative dose is the actual total dose administered.	Up to 2 years
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
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
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
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	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
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
Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause		Up to 2 years

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: May 21, 2009
• First Submitted That Met QC Criteria: May 28, 2009
• First Posted (Estimate): May 29, 2009

Study Record Updates

• Last Update Posted (Actual): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Endometrial cancer; Antitumour efficacy in women with advanced endometrial cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Appetite Stimulants; Megestrol; Megestrol Acetate
• Other Study ID Numbers: X-55-58064-004; 2009-010613-68 (EudraCT Number)