Endometrial Cancer
Conditions
Keywords
Endometrial cancer, Antitumour efficacy in women with advanced endometrial cancer
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.
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.
Interventions
DRUGBN83495
BN83495 will be administered as a 40 mg tablet once a day orally
DRUGMegestrol Acetate (MA)
MA will be administered orally as 160mg daily
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Tolerability of BN83495 Based on Length of Exposure | Up to 2 years | Length of exposure includes interruptions. |
| Tolerability of BN83495 Based on Cumulative Dose Administered | Up to 2 years | Cumulative dose is the actual total dose administered. |
| 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. |
| 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. |
| 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. |
| Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation | Up to 2 years | — |
| 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. |
| 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. |
| Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause | Up to 2 years | — |
| Percentage of Participants With Overall Response (OR) Including CR and PR | Up to 2 years | — |
Countries
Belgium, Czechia, France, Hungary, Latvia, Lithuania, Moldova, Poland, Russia, Spain, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: BN83495 40 mg BN83495 (Irosustat) 40 mg tablet by mouth once daily | 36 |
| Arm B: MA 160 mg MA 160 mg tablet by mouth once daily | 37 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Pre-assignment | Withdrawal by Subject | 0 | 2 |
| Treatment and Survival | Adverse Event | 1 | 0 |
| Treatment and Survival | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Arm A: BN83495 40 mg | Arm B: MA 160 mg | Total |
|---|---|---|---|
| Age, Continuous | 68.1 Years STANDARD_DEVIATION 11.4 | 67.4 Years STANDARD_DEVIATION 8.6 | 67.7 Years STANDARD_DEVIATION 10 |
| Age, Customized 18-64 years | 12 Participants | 16 Participants | 28 Participants |
| Age, Customized 65-75 years | 13 Participants | 15 Participants | 28 Participants |
| Age, Customized >75 years | 11 Participants | 6 Participants | 17 Participants |
| BMI (Body Mass Index) 18.5 - 25 kg/m2 | 10 Participants | 10 Participants | 20 Participants |
| BMI (Body Mass Index) <18.5 kg/m2 | 1 Participants | 0 Participants | 1 Participants |
| BMI (Body Mass Index) >25 - 30 kg/m2 | 10 Participants | 8 Participants | 18 Participants |
| BMI (Body Mass Index) >30 kg/m2 | 12 Participants | 17 Participants | 29 Participants |
| BMI (Body Mass Index) Missing | 3 Participants | 2 Participants | 5 Participants |
| Eastern Cooperative Oncology Group(ECOG) Performance Status Score | 0.8 Units on a scale STANDARD_DEVIATION 0.6 | 0.7 Units on a scale STANDARD_DEVIATION 0.7 | 0.7 Units on a scale STANDARD_DEVIATION 0.7 |
| Race Black / African American | 0 Subjects | 1 Subjects | 1 Subjects |
| Race Caucasian / White | 36 Subjects | 36 Subjects | 72 Subjects |
| Region of Enrollment Belgium | 6 Participants | 2 Participants | 8 Participants |
| Region of Enrollment Czech Republic | 3 Participants | 5 Participants | 8 Participants |
| Region of Enrollment France | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment Latvia | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Lithuania | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Moldova, Republic of | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Poland | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Russian Federation | 6 Participants | 8 Participants | 14 Participants |
| Region of Enrollment Spain | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Ukraine | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 7 Participants | 14 Participants |
| Sex/Gender, Customized Female | 36 Participants | 37 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 36 | 29 / 35 |
| serious Total, serious adverse events | 9 / 36 | 6 / 35 |
Outcome results
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).
Time frame: Up to 6 months
Population: Intent-to-treat (ITT) population includes all randomized subjects who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: BN83495 40 mg | Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died | 36.1 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Women With Advanced or Recurrent Endometrial Cancer Who Have Neither Progressed Nor Died | 54.1 Percentage of subjects |
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.
Time frame: At 2 years
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: BN83495 40 mg | Duration of Response (DR) in Responders | NA Weeks |
| Arm B: MA 160 mg | Duration of Response (DR) in Responders | 105.14 Weeks |
p-value: 0.698Kaplan-Meier Analysis
Secondary
Overall Survival (OS)
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
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: BN83495 40 mg | Overall Survival (OS) | 63.43 Weeks |
| Arm B: MA 160 mg | Overall Survival (OS) | NA Weeks |
p-value: 0.3078Kaplan-Meier Analysis
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.
Time frame: Up to week 32
Population: ITT population.~Three subjects withdrawn the consent from MA 160 mg group and did not have EuroQoL score up to week 32.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 2 | 54.2 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 4 | 54.2 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 8 | 25.0 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 16 | 25.0 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 24 | 16.7 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 32 | 16.7 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 2 | 0.0 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 4 | 4.2 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 8 | 4.2 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 16 | 0.0 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 24 | 0.0 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 32 | 8.3 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 2 | 20.8 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 4 | 16.7 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 8 | 16.7 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 16 | 12.5 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 24 | 12.5 Percentage of participants |
| Arm A: BN83495 40 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 32 | 0.0 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 4 | 16.7 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 2 | 50.0 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 16 | 0.0 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 4 | 61.1 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 32 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 8 | 50.0 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 24 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 16 | 50.0 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 8 | 16.7 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 24 | 33.3 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 32 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | No Change or Deterioration at week 32 | 22.2 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 24 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 2 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 2 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 4 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of ≥10% at week 16 | 5.6 Percentage of participants |
| Arm B: MA 160 mg | Percentage of Participants >65 Years of Age With No Change or Deterioration, Improvement of <10%, or Improvement of ≥10% on the EuroQoL Score | Improvement of <10% at week 8 | 5.6 Percentage of participants |
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
Time frame: Up to Day 28 follow-up
Population: Safety Population: All randomised subjects who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 5 | 2.8 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Missing | 5.6 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 3 | 22.2 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Causality of TEAEs - Related | 55.6 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Any Treatment Emergent AEs (TEAEs) | 88.9 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Causality of TEAEs - Not related | 77.8 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 2 | 63.9 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | TEAEs Leading to Withdrawal | 8.3 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 4 | 5.6 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | TEAEs Leading to Death | 2.8 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 1 | 80.6 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Serious Adverse Events (SAEs) | 25.0 Percentage of subjects |
| Arm A: BN83495 40 mg | Percentage of Participants With Adverse Event (AE) | Any AEs | 88.9 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Serious Adverse Events (SAEs) | 17.1 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Any AEs | 82.9 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Any Treatment Emergent AEs (TEAEs) | 82.9 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 5 | 2.9 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 4 | 0.0 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 3 | 25.7 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 2 | 45.7 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Grade 1 | 74.3 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Intensity of TEAEs - Missing | 0.0 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Causality of TEAEs - Related | 37.1 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | Causality of TEAEs - Not related | 77.1 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | TEAEs Leading to Withdrawal | 2.9 Percentage of subjects |
| Arm B: MA 160 mg | Percentage of Participants With Adverse Event (AE) | TEAEs Leading to Death | 2.9 Percentage of subjects |
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.
Time frame: Up to 2 years
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: BN83495 40 mg | Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks | 13 Percentage of Participants | Standard Deviation 36.1 |
| Arm B: MA 160 mg | Percentage of Participants With Clinical Benefit [Including Completed Response (CR), Partial Response (PR), and Stable Disease (SD)] ≥12 Weeks | 19 Percentage of Participants | Standard Deviation 51.4 |
p-value: 0.1895Kaplan-Meier Analysis
Secondary
Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation
Time frame: Up to 2 years
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: BN83495 40 mg | Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation | 30 Percentage of Participants | Standard Deviation 83.3 |
| Arm B: MA 160 mg | Percentage of Participants With First Documentation of Objective Tumour Progression From Randomisation | 24 Percentage of Participants | Standard Deviation 64.9 |
Secondary
Percentage of Participants With Overall Response (OR) Including CR and PR
Time frame: Up to 2 years
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: BN83495 40 mg | Percentage of Participants With Overall Response (OR) Including CR and PR | 3 Percentage of Participants | Standard Deviation 8.3 |
| Arm B: MA 160 mg | Percentage of Participants With Overall Response (OR) Including CR and PR | 11 Percentage of Participants | Standard Deviation 29.7 |
p-value: 0.0203Kaplan-Meier Analysis
Secondary
Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: BN83495 40 mg | Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause | 16.14 Weeks |
| Arm B: MA 160 mg | Progression Free Survival (PFS): Time From Randomisation Until Objective Tumour Progression or Death From Any Cause | 40.14 Weeks |
p-value: 0.0484Kaplan-Meier Analysis
Secondary
Tolerability of BN83495 Based on Cumulative Dose Administered
Cumulative dose is the actual total dose administered.
Time frame: Up to 2 years
Population: Safety Population~Missing number of subjects = 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: BN83495 40 mg | Tolerability of BN83495 Based on Cumulative Dose Administered | 9452.22 mg | Standard Deviation 10799.16 |
| Arm B: MA 160 mg | Tolerability of BN83495 Based on Cumulative Dose Administered | 60703.03 mg | Standard Deviation 51726.14 |
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.
Time frame: Up to 2 years
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: BN83495 40 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Reason for Interruptions (AE) | 16.7 Percentage of participants |
| Arm A: BN83495 40 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Dose Interruptions | 27.8 Percentage of participants |
| Arm A: BN83495 40 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Reason for Interruptions (Treatment forgotten) | 0.0 Percentage of participants |
| Arm A: BN83495 40 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Reason for Interruptions (Other) | 13.9 Percentage of participants |
| Arm B: MA 160 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Reason for Interruptions (Other) | 20.0 Percentage of participants |
| Arm B: MA 160 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Reason for Interruptions (Treatment forgotten) | 8.6 Percentage of participants |
| Arm B: MA 160 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Dose Interruptions | 34.5 Percentage of participants |
| Arm B: MA 160 mg | Tolerability of BN83495 Based on Dose Interruptions and Reason for Interruptions | Reason for Interruptions (AE) | 8.6 Percentage of participants |
Secondary
Tolerability of BN83495 Based on Length of Exposure
Length of exposure includes interruptions.
Time frame: Up to 2 years
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: BN83495 40 mg | Tolerability of BN83495 Based on Length of Exposure | 34.94 Week | Standard Deviation 38.85 |
| Arm B: MA 160 mg | Tolerability of BN83495 Based on Length of Exposure | 55.20 Week | Standard Deviation 49.48 |