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

This study has been completed.
Information provided by (Responsible Party):
Ipsen Identifier:
First received: May 21, 2009
Last updated: August 28, 2015
Last verified: August 2015
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.

Condition Intervention Phase
Endometrial Cancer
Drug: BN83495
Drug: Megestrol Acetate (MA)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Ipsen:

Primary Outcome Measures:
  • Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants With Adverse Event (AE) [ Time Frame: Up to Day 28 follow-up ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Length of exposure includes interruptions.

  • Tolerability of BN83495 Based on Cumulative Dose Administered [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Cumulative dose is the actual total dose administered.

  • Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Percentage of participants who had dose interruptions and reason for interruptions as AE, study treatment forgotten, and other reasons.

  • Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score [ Time Frame: Up to week 32 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Duration of Response (DR) in Responders [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) [ Time Frame: At 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: August 2009
Study Completion Date: July 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

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

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
  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 identifier: NCT00910091

  Show 54 Study Locations
Sponsors and Collaborators
Study Director: Eric Chetaille, MD Ipsen
  More Information

No publications provided

Responsible Party: Ipsen Identifier: NCT00910091     History of Changes
Other Study ID Numbers: X-55-58064-004, 2009-010613-68
Study First Received: May 21, 2009
Results First Received: July 17, 2015
Last Updated: August 28, 2015
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Moldova: Agentia Medicamentului
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: AEMPS, Agencia Española de Medicamentos y Productos Sanitarios
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Hungary: National Institute of Pharmacy
Lithuania: State Medicine Control Agency - Ministry of Health
Latvia: State Agency of Medicines

Keywords provided by Ipsen:
Endometrial cancer
Antitumour efficacy in women with advanced endometrial cancer

Additional relevant MeSH terms:
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Megestrol Acetate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Appetite Stimulants
Central Nervous System Agents
Central Nervous System Stimulants
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses processed this record on November 27, 2015