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

• Sponsor: Ipsen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00910091
• Collaborator: (none)
• Enrollment: 73
• Locations: 54
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer	Drug: BN83495; Drug: Megestrol Acetate (MA)	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. Tolerability of BN83495 Based on Length of Exposure [Up to 2 years]

   Length of exposure includes interruptions.

3. Tolerability of BN83495 Based on Cumulative Dose Administered [Up to 2 years]

   Cumulative dose is the actual total dose administered.

4. 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.

5. 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.

6. 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.

7. Percentage of Participants With Overall Response (OR) Including CR and PR [Up to 2 years]

8. Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation [Up to 2 years]

9. 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.

10. 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.

11. Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause [Up to 2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes 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

Locations

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

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT00910091
• Other Study ID Numbers: X-55-58064-004; 2009-010613-68
• First Posted: May 29, 2009
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Ipsen: Endometrial cancer; Antitumour efficacy in women with advanced endometrial cancer
• Additional relevant MeSH terms: Endometrial Neoplasms; Megestrol; Megestrol Acetate

Study Results

Participant Flow

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	Megestrol Acetate (MA) 160 mg tablet by mouth once daily
Period Title: Pre-assignment
STARTED	36	37
COMPLETED	36	35
NOT COMPLETED	0	2
Period Title: Pre-assignment
STARTED	36	35
COMPLETED	32	31
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg	Total
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily	Total of all reporting groups
Overall Participants	36	37	73
Age (Years) [Median (Standard Deviation) ]
Median (Standard Deviation) [Years]	68.1 (11.4)	67.4 (8.6)	67.7 (10.0)
Age, Customized (Number) [Number]
18-64 years	12 33.3%	16 43.2%	28 38.4%
65-75 years	13 36.1%	15 40.5%	28 38.4%
>75 years	11 30.6%	6 16.2%	17 23.3%
Sex/Gender, Customized (Number) [Number]
Female	36 100%	37 100%	73 100%
Region of Enrollment (Number) [Number]
France	8 22.2%	7 18.9%	15 20.5%
United Kingdom	7 19.4%	7 18.9%	14 19.2%
Belgium	6 16.7%	2 5.4%	8 11%
Russian Federation	6 16.7%	8 21.6%	14 19.2%
Czech Republic	3 8.3%	5 13.5%	8 11%
Poland	2 5.6%	2 5.4%	4 5.5%
Ukraine	2 5.6%	2 5.4%	4 5.5%
Lithuania	1 2.8%	1 2.7%	2 2.7%
Spain	1 2.8%	1 2.7%	2 2.7%
Latvia	0 0%	1 2.7%	1 1.4%
Moldova, Republic of	0 0%	1 2.7%	1 1.4%
BMI (Body Mass Index) (Number) [Number]
<18.5 kg/m2	1 2.8%	0 0%	1 1.4%
18.5 - 25 kg/m2	10 27.8%	10 27%	20 27.4%
>25 - 30 kg/m2	10 27.8%	8 21.6%	18 24.7%
>30 kg/m2	12 33.3%	17 45.9%	29 39.7%
Missing	3 8.3%	2 5.4%	5 6.8%
Race (Subjects) [Number]
Black / African American	0	1	1
Caucasian / White	36	36	72
Eastern Cooperative Oncology Group(ECOG) Performance Status Score (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	0.8 (0.6)	0.7 (0.7)	0.7 (0.7)

Outcome Measures

1. Primary Outcome

Title	Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died
Description	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).
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population includes all randomized subjects who received at least one dose of study medication.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Number (90% Confidence Interval) [Percentage of subjects]	36.1	54.1

2. Secondary Outcome

Title	Percentage of Participants With Adverse Event (AE)
Description	Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening/disabling and Grade 5: Death
Time Frame	Up to Day 28 follow-up

Outcome Measure Data

Analysis Population Description

Safety Population: All randomised subjects who received at least one dose of study medication.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	Megestrol Acetate (MA) 160 mg tablet by mouth once daily
Measure Participants	36	35
Any AEs	88.9	82.9
Any Treatment Emergent AEs (TEAEs)	88.9	82.9
Intensity of TEAEs - Grade 5	2.8	2.9
Intensity of TEAEs - Grade 4	5.6	0.0
Intensity of TEAEs - Grade 3	22.2	25.7
Intensity of TEAEs - Grade 2	63.9	45.7
Intensity of TEAEs - Grade 1	80.6	74.3
Intensity of TEAEs - Missing	5.6	0.0
Causality of TEAEs - Related	55.6	37.1
Causality of TEAEs - Not related	77.8	77.1
TEAEs Leading to Withdrawal	8.3	2.9
TEAEs Leading to Death	2.8	2.9
Serious Adverse Events (SAEs)	25.0	17.1

3. Secondary Outcome

Title	Tolerability of BN83495 Based on Length of Exposure
Description	Length of exposure includes interruptions.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	35
Mean (Standard Deviation) [Week]	34.94 (38.85)	55.20 (49.48)

4. Secondary Outcome

Title	Tolerability of BN83495 Based on Cumulative Dose Administered
Description	Cumulative dose is the actual total dose administered.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Safety Population Missing number of subjects = 2

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	33
Mean (Standard Deviation) [mg]	9452.22 (10799.16)	60703.03 (51726.14)

5. Secondary Outcome

Title	Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions
Description	Percentage of participants who had dose interruptions and reason for interruptions as AE, study treatment forgotten, and other reasons.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	35
Dose Interruptions	27.8 77.2%	34.5 93.2%
Reason for Interruptions (AE)	16.7 46.4%	8.6 23.2%
Reason for Interruptions (Treatment forgotten)	0.0 0%	8.6 23.2%
Reason for Interruptions (Other)	13.9 38.6%	20.0 54.1%

6. Secondary Outcome

Title	Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score
Description	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.
Time Frame	Up to week 32

Outcome Measure Data

Analysis Population Description

ITT population. Three subjects withdrawn the consent from MA 160 mg group and did not have EuroQoL score up to week 32.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	24	18
No Change or Deterioration at week 2	54.2 150.6%	50.0 135.1%
No Change or Deterioration at week 4	54.2 150.6%	61.1 165.1%
No Change or Deterioration at week 8	25.0 69.4%	50.0 135.1%
No Change or Deterioration at week 16	25.0 69.4%	50.0 135.1%
No Change or Deterioration at week 24	16.7 46.4%	33.3 90%
No Change or Deterioration at week 32	16.7 46.4%	22.2 60%
Improvement of <10% at week 2	0.0 0%	5.6 15.1%
Improvement of <10% at week 4	4.2 11.7%	5.6 15.1%
Improvement of <10% at week 8	4.2 11.7%	5.6 15.1%
Improvement of <10% at week 16	0.0 0%	0.0 0%
Improvement of <10% at week 24	0.0 0%	5.6 15.1%
Improvement of <10% at week 32	8.3 23.1%	5.6 15.1%
Improvement of ≥10% at week 2	20.8 57.8%	5.6 15.1%
Improvement of ≥10% at week 4	16.7 46.4%	16.7 45.1%
Improvement of ≥10% at week 8	16.7 46.4%	16.7 45.1%
Improvement of ≥10% at week 16	12.5 34.7%	5.6 15.1%
Improvement of ≥10% at week 24	12.5 34.7%	5.6 15.1%
Improvement of ≥10% at week 32	0.0 0%	5.6 15.1%

7. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Mean (Standard Deviation) [Percentage of Participants]	13 (36.1) 36.1%	19 (51.4) 51.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: BN83495 40 mg, Arm B: MA 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1895
	Comments
	Method	Kaplan-Meier Analysis
	Comments

8. Secondary Outcome

Title	Percentage of Participants With Overall Response (OR) Including CR and PR
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Mean (Standard Deviation) [Percentage of Participants]	3 (8.3) 8.3%	11 (29.7) 29.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: BN83495 40 mg, Arm B: MA 160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0203
	Comments
	Method	Kaplan-Meier Analysis
	Comments

9. Secondary Outcome

Title	Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Mean (Standard Deviation) [Percentage of Participants]	30 (83.3) 83.3%	24 (64.9) 64.9%

10. Secondary Outcome

Title	Duration of Response (DR) in Responders
Description	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.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Median (90% Confidence Interval) [Weeks]	NA	105.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: BN83495 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6980
	Comments
	Method	Kaplan-Meier Analysis
	Comments

11. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from the date of enrollment to the date of death due to any cause.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Median (90% Confidence Interval) [Weeks]	63.43	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: BN83495 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3078
	Comments
	Method	Kaplan-Meier Analysis
	Comments

12. Secondary Outcome

Title	Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: BN83495 40 mg	Arm B: MA 160 mg
Arm/Group Description	BN83495 (Irosustat) 40 mg tablet by mouth once daily	MA 160 mg tablet by mouth once daily
Measure Participants	36	37
Median (90% Confidence Interval) [Weeks]	16.14	40.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: BN83495 40 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0484
	Comments
	Method	Kaplan-Meier Analysis
	Comments

Adverse Events

Time Frame	Up to Day 28 follow-up
Arm/Group Title	A- BN 83495- 40mg		B- MA - 160mg
Arm/Group Description	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 BN83495: BN83495 will be administered as a 40 mg tablet once a day orally		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 Megestrol Acetate (MA): MA will be administered orally as 160mg daily
All Cause Mortality
	A- BN 83495- 40mg		B- MA - 160mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	A- BN 83495- 40mg		B- MA - 160mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/36 (25%)		6/35 (17.1%)
Blood and lymphatic system disorders
Anaemia	2/36 (5.6%)	2	0/35 (0%)	0
Cardiac disorders
Acute Myocardial Infarction	1/36 (2.8%)	1	0/35 (0%)	0
Gastrointestinal disorders
Vomiting	2/36 (5.6%)	2	1/35 (2.9%)	1
Constipation	1/36 (2.8%)	1	0/35 (0%)	0
Abdominal Pain Upper	0/36 (0%)	0	1/35 (2.9%)	2
Diarrhoea	0/36 (0%)	0	1/35 (2.9%)	1
General disorders
Asthenia	2/36 (5.6%)	2	0/35 (0%)	0
Infections and infestations
Lower Respiratory Tract Infection	1/36 (2.8%)	1	0/35 (0%)	0
Metabolism and nutrition disorders
Decreased Appetite	1/36 (2.8%)	1	0/35 (0%)	0
Diabetes Mellitus Inadequate Control	1/36 (2.8%)	1	0/35 (0%)	0
Hyponatraemia	1/36 (2.8%)	1	0/35 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Neoplasm Malignant	1/36 (2.8%)	2	0/35 (0%)	0
Tumour Haemorrhage	1/36 (2.8%)	1	0/35 (0%)	0
Renal and urinary disorders
Haematuria	1/36 (2.8%)	1	0/35 (0%)	0
Nephrolithiasis	1/36 (2.8%)	1	0/35 (0%)	0
Renal Failure Acute	1/36 (2.8%)	1	0/35 (0%)	0
Urinary Retention	0/36 (0%)	0	2/35 (5.7%)	2
Reproductive system and breast disorders
Pelvic Pain	0/36 (0%)	0	1/35 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/36 (2.8%)	1	0/35 (0%)	0
Dyspnoea	0/36 (0%)	0	1/35 (2.9%)	1
Pleural Effusion	0/36 (0%)	0	1/35 (2.9%)	1
Pulmonary Embolism	0/36 (0%)	0	2/35 (5.7%)	2
Other (Not Including Serious) Adverse Events
	A- BN 83495- 40mg		B- MA - 160mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/36 (88.9%)		29/35 (82.9%)
Blood and lymphatic system disorders
Anaemia	4/36 (11.1%)	4	2/35 (5.7%)	2
Gastrointestinal disorders
Nausea	7/36 (19.4%)	7	3/35 (8.6%)	3
Vomiting	6/36 (16.7%)	6	4/35 (11.4%)	4
Constipation	5/36 (13.9%)	5	4/35 (11.4%)	4
Diarrhoea	5/36 (13.9%)	5	6/35 (17.1%)	6
Abdominal Pain	2/36 (5.6%)	2	1/35 (2.9%)	1
Abdominal Pain Upper	1/36 (2.8%)	1	2/35 (5.7%)	2
Dry Mouth	1/36 (2.8%)	1	2/35 (5.7%)	2
Dyspepsia	1/36 (2.8%)	1	3/35 (8.6%)	3
General disorders
Asthenia	6/36 (16.7%)	6	2/35 (5.7%)	2
Fatigue	6/36 (16.7%)	6	4/35 (11.4%)	4
Spinal Pain	2/36 (5.6%)	2	0/35 (0%)	0
Oedema Peripheral	0/36 (0%)	0	2/35 (5.7%)	2
Immune system disorders
Contrast Media Allergy	0/36 (0%)	0	2/35 (5.7%)	2
Infections and infestations
Lower Respiratory Tract Infection	2/36 (5.6%)	2	0/35 (0%)	0
Cystitis	1/36 (2.8%)	1	2/35 (5.7%)	2
Urinary Tract Infection	1/36 (2.8%)	1	6/35 (17.1%)	6
Injury, poisoning and procedural complications
Fall	0/36 (0%)	0	2/35 (5.7%)	2
Investigations
Blood Creatinine Increased	3/36 (8.3%)	3	1/35 (2.9%)	1
Blood Urea Increased	2/36 (5.6%)	2	0/35 (0%)	0
Blood Lactate Dehydrogenase Increased	0/36 (0%)	0	2/35 (5.7%)	2
Metabolism and nutrition disorders
Decreased Appetite	3/36 (8.3%)	3	1/35 (2.9%)	1
Dehydration	2/36 (5.6%)	2	0/35 (0%)	0
Hypocalcaemia	2/36 (5.6%)	2	1/35 (2.9%)	1
Hypokalaemia	2/36 (5.6%)	2	2/35 (5.7%)	2
Hypercholesterolaemia	0/36 (0%)	0	2/35 (5.7%)	2
Hyperglycaemia	0/36 (0%)	0	2/35 (5.7%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/36 (5.6%)	2	2/35 (5.7%)	2
Muscle Spasms	2/36 (5.6%)	2	0/35 (0%)	0
Musculoskeletal Chest Pain	2/36 (5.6%)	2	0/35 (0%)	0
Musculoskeletal Pain	2/36 (5.6%)	2	1/35 (2.9%)	1
Back Pain	1/36 (2.8%)	1	2/35 (5.7%)	2
Osteoarthritis	0/36 (0%)	0	2/35 (5.7%)	2
Nervous system disorders
Headache	3/36 (8.3%)	3	1/35 (2.9%)	1
Dysgeusia	1/36 (2.8%)	1	2/35 (5.7%)	2
Lethargy	1/36 (2.8%)	1	2/35 (5.7%)	2
Psychiatric disorders
Depression	1/36 (2.8%)	1	2/35 (5.7%)	2
Renal and urinary disorders
Dysuria	1/36 (2.8%)	1	2/35 (5.7%)	2
Urinary Incontinence	0/36 (0%)	0	2/35 (5.7%)	2
Urinary Retention	0/36 (0%)	0	2/35 (5.7%)	2
Reproductive system and breast disorders
Vaginal Haemorrhage	2/36 (5.6%)	2	0/35 (0%)	0
Pelvic Pain	0/36 (0%)	0	2/35 (5.7%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/36 (8.3%)	3	5/35 (14.3%)	5
Cough	2/36 (5.6%)	2	2/35 (5.7%)	2
Pulmonary Embolism	0/36 (0%)	0	2/35 (5.7%)	2
Skin and subcutaneous tissue disorders
Dry Skin	14/36 (38.9%)	14	5/35 (14.3%)	5
Rash	1/36 (2.8%)	1	2/35 (5.7%)	2
Skin Fissures	0/36 (0%)	0	2/35 (5.7%)	2
Urticaria	0/36 (0%)	0	2/35 (5.7%)	2
Vascular disorders
Hypertension	2/36 (5.6%)	2	4/35 (11.4%)	4
Hot Flush	0/36 (0%)	0	3/35 (8.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.