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.

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.

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