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Trial record 46 of 103 for:    "Kennedy disease"

A Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2 Positive (HER2+), Androgen Receptor Positive (AR+) Metastatic or Locally Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02091960
Recruitment Status : Active, not recruiting
First Posted : March 19, 2014
Results First Posted : May 16, 2018
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions HER2 Amplified
Advanced Breast Cancer
Human Epidermal Growth Factor Receptor 2 (HER2)
Interventions Drug: Enzalutamide
Drug: Trastuzumab
Enrollment 103
Recruitment Details The study was conducted at 35 clinical sites in Belgium, Canada, Italy, Spain, the United Kingdom and the United States.
Pre-assignment Details

This study enrolled women with human epidermal growth factor receptor 2 positive (HER2+) and androgen receptor positive (AR+) metastatic or locally advanced breast cancer who progressed on anti-HER2 therapy in the metastatic or advanced setting.

The study is ongoing, results are reported as of the data cut off date of 28 February 2017.

Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Period Title: Overall Study
Started 103
Received Treatment 103
Completed 52 [1]
Not Completed 51
Reason Not Completed
Death             7
Withdrawal by Subject             1
Miscellaneous Reasons             31
On Study at Data Cut-off             12
[1]
Completed indicates participants with disease progression
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Baseline Participants 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants
59.3  (10.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Female
103
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Hispanic or Latino
5
   4.9%
Not Hispanic or Latino
98
  95.1%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 103 participants
White
90
  87.4%
Black or African American
8
   7.8%
Asian
3
   2.9%
American Indian or Alaskan Native
0
   0.0%
Native Hawaiian or other Pacific Islander
1
   1.0%
Other
1
   1.0%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Grade 0
51
  49.5%
Grade 1
51
  49.5%
Missing
1
   1.0%
[1]
Measure Description: A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.
Time from Initial Diagnosis of Primary Cancer to Enrollment   [1] 
Median (Full Range)
Unit of measure:  Days
Number Analyzed 95 participants
1199
(30 to 4713)
[1]
Measure Analysis Population Description: Participants for whom data were available
Histopathology at Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Ductal
73
  70.9%
Inflammatory
5
   4.9%
Intraductal
6
   5.8%
Lobular
6
   5.8%
Mixed
1
   1.0%
Not otherwise specified
1
   1.0%
Other
5
   4.9%
Unknown
6
   5.8%
Anatomic Stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants
Stage 0
3
   2.9%
Stage IA
6
   5.8%
Stage IB
1
   1.0%
Stage IIA
14
  13.6%
Stage IIB
12
  11.7%
Stage IIIA
5
   4.9%
Stage IIIB
7
   6.8%
Stage IIIC
7
   6.8%
Stage IV
28
  27.2%
Unknown
20
  19.4%
[1]
Measure Description:

Breast cancer staging is based on size of the tumor, whether cancer cells have spread to lymph nodes or to other parts of the body, how aggressive the cells appear when viewed under a microscope, whether the cancer cells have receptors for estrogen and progesterone or have a gene mutation that causes them to make excess HER2 protein, and the results of gene expression profiling tests.

The stages of breast cancer range from 0 to IV, where Stage 0 is noninvasive or contained within the milk ducts and Stage IV breast cancer, also called metastatic, has spread to other areas of the body.

1.Primary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description

Clinical benefit rate was defined as the percentage of evaluable participants with best objective response of confirmed complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or prolonged stable disease (≥ 24 weeks).

Complete response (CR) was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all < 10 mm in short axis.

Partial response (PR) was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions, with persistence of non-target lesions and no new lesions.

Stable disease (SD) was defined as < 30% decrease and < 20% increase in the size of target lesions, persistence of non-target lesions, and no new lesions.

PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date that PR or CR was first observed. SD required confirmation with equivalent or improved assessment no less than 8 weeks after enrollment.

Time Frame Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression, initiation of new therapy or withdrawal of consent. The median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy evaluable set (EES) includes all enrolled participants who had centrally assessed androgen receptor positive (AR+; defined as ≥ 10% of tumor cells with nuclear expression), received at least one dose of study drug, and had at least one available post baseline tumor assessment.
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
23.6
(15.2 to 33.8)
2.Secondary Outcome
Title Overall Response Rate at Week 24
Hide Description

Overall response rate was defined as the percentage of evaluable participants with a best objective response of confirmed complete response (CR) or partial response (PR) per RECIST 1.1.

Complete response was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all < 10 mm in short axis.

Partial response was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions with persistence of non-target lesions and no new lesions.

PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date of scan that PR or CR was first observed.

Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable set
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.4
(0.7 to 9.5)
3.Secondary Outcome
Title Best Overall Response Rate
Hide Description

Best overall response was the best response across all time points, based on investigator assessments.

Best overall response rate was defined as the percentage of evaluable participants with a best objective response of confirmed complete response (CR) or partial response (PR) at any time during the study per RECIST 1.1.

Complete response was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all < 10 mm in short axis.

Partial response was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions with persistence of non-target lesions and no new lesions.

PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date of scan that PR or CR was first observed.

Time Frame Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression, initiation of new therapy or withdrawal of consent. The median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable set
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.5
(1.2 to 11.1)
4.Secondary Outcome
Title Progression-free Survival
Hide Description

Progression-free survival was defined as the time from the date of first dose of enzalutamide until the date of disease progression per RECIST 1.1, or death from any cause on study, whichever occurred first. Participants who initiated another antitumor therapy before documented progressive disease (PD) or death, or who progressed or died after missing 2 or more consecutive radiological assessments were censored at the date of the last radiological assessment showing no progression.

Progressive disease was defined as a ≥ 20% increase in the size of target lesions and at least a 5 mm increase in size of target lesions from smallest size on study, or unequivocal progression of non-target lesions, or any new lesions.

Time Frame From the date of first dose of study drug to the data cut-off date of 28 February 2017; the median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable set
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 89
Median (95% Confidence Interval)
Unit of Measure: days
105.0
(61 to 116)
5.Secondary Outcome
Title Time to Progression
Hide Description Time to progression was defined as the time from the first date of enzalutamide treatment until the date of disease progression per RECIST 1.1. Participants who initiated another anti-tumor therapy before documented PD, who progressed after missing two or more consecutive radiological assessments or who died before disease progression were censored at the date of the last radiological assessment showing no progression.
Time Frame From the date of first dose of study drug to the data cut-off date of 28 February 2017; the median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis set
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 89
Median (Full Range)
Unit of Measure: days
108.0
(61 to 116)
6.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the time from the date of first documentation of response (CR or PR) until the date of disease progression per RECIST 1.1. Participants who initiated another anti-tumor therapy before documented PD, progressed after missing two or more consecutive radiological assessments or who died before disease progression were censored at the date of the last radiological assessment showing no progression.
Time Frame Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression, initiation of new therapy or withdrawal of consent. The median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable set participants with a best overall response of CR or PR
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 4
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
[1]
Could not be estimated due to the low number of events
7.Secondary Outcome
Title Time to Response
Hide Description Time to response was defined as the time from the first date of enzalutamide treatment to initial CR or PR and was calculated for participants with a CR or PR.
Time Frame From the date of first dose of study drug to the data cut-off date of 28 February 2017; the median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy evaluable set with a best overall response of CR or PR
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 4
Median (95% Confidence Interval)
Unit of Measure: days
57
(57 to 222)
8.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description

An AE was defined as any untoward medical occurrence in a patient administered study drug or who underwent study procedures and did not necessarily have a causal relationship with treatment. An abnormality identified during a medical test was defined as an AE only if the abnormality induced clinical signs or symptoms, required active intervention, required interruption or discontinuation of study medication, or was clinically significant in the opinion of the investigator.

An AE was defined as serious if it resulted in any of the following outcomes:

  • Death
  • Was life-threatening
  • Persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions
  • Congenital anomaly, or birth defect
  • Inpatient hospitalization or prolongation of hospitalization
  • Other medically important event. Drug-related AEs were those assessed by the investigator as AEs whose relationship to the to the study drugs could not be ruled out.
Time Frame From the first dose date of study drug to 30 days after the last dose date of study drug or the start of subsequent treatment or date of death, whichever was first; median duration of treatment was 70 days, and the maximum was 660 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 or partial dose of study drug.
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description:
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Overall Number of Participants Analyzed 103
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse events (AE)
97
  94.2%
AE related to enzalutamide
75
  72.8%
AE related to trastuzumab
39
  37.9%
Any drug-related AE
78
  75.7%
Deaths
4
   3.9%
Serious adverse events (SAE)
22
  21.4%
SAE related to enzalutamide
3
   2.9%
SAE related to trastuzumab
0
   0.0%
Any drug-related SAE
3
   2.9%
AE leading to discontinuation of enzalutamide
20
  19.4%
AE leading to discontinuation of trastuzumab
18
  17.5%
AE leading to discontinuation of any study drug
21
  20.4%
Enzalutamide-related leading to discontinuation
5
   4.9%
Trastuzumab-related AE leading to discontinuation
4
   3.9%
Any drug-related AE leading to discontinuation
8
   7.8%
AE leading to dose reduction
7
   6.8%
AE leading to dose interruption
23
  22.3%
Time Frame From the first dose date of study drug to 30 days after the last dose date of study drug or the start of subsequent treatment or date of death, whichever was first; median duration of treatment was 70 days, and the maximum was 660 days. All-cause mortality data includes deaths that occurred more than 30 days after last dose, up to the data cutoff date of 28 February 2017.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Enzalutamide + Trastuzumab
Hide Arm/Group Description Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
All-Cause Mortality
Enzalutamide + Trastuzumab
Affected / at Risk (%)
Total   7/103 (6.80%)    
Show Serious Adverse Events Hide Serious Adverse Events
Enzalutamide + Trastuzumab
Affected / at Risk (%) # Events
Total   22/103 (21.36%)    
Gastrointestinal disorders   
Abdominal pain  1  2/103 (1.94%)  2
Diarrhoea  1  1/103 (0.97%)  1
Dyspepsia  1  1/103 (0.97%)  1
Nausea  1  3/103 (2.91%)  4
Vomiting  1  3/103 (2.91%)  4
General disorders   
Asthenia  1  1/103 (0.97%)  1
General physical health deterioration  1  1/103 (0.97%)  1
Pyrexia  1  1/103 (0.97%)  1
Infections and infestations   
Escherichia urinary tract infection  1  1/103 (0.97%)  1
Infection  1  1/103 (0.97%)  2
Pneumonia  1  2/103 (1.94%)  2
Injury, poisoning and procedural complications   
Accidental overdose  1  1/103 (0.97%)  1
Spinal compression fracture  1  1/103 (0.97%)  2
Musculoskeletal and connective tissue disorders   
Back pain  1  2/103 (1.94%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression  1  5/103 (4.85%)  6
Metastases to skin  1  1/103 (0.97%)  1
Skin cancer  1  1/103 (0.97%)  1
Skin neoplasm bleeding  1  1/103 (0.97%)  1
Renal and urinary disorders   
Hydronephrosis  1  1/103 (0.97%)  1
Urinary retention  1  1/103 (0.97%)  1
Reproductive system and breast disorders   
Vaginal haemorrhage  1  1/103 (0.97%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  2/103 (1.94%)  2
Pleural effusion  1  1/103 (0.97%)  1
Pulmonary oedema  1  1/103 (0.97%)  1
Vascular disorders   
Embolism  1  1/103 (0.97%)  1
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Enzalutamide + Trastuzumab
Affected / at Risk (%) # Events
Total   87/103 (84.47%)    
Blood and lymphatic system disorders   
Anaemia  1  9/103 (8.74%)  10
Gastrointestinal disorders   
Constipation  1  13/103 (12.62%)  14
Diarrhoea  1  13/103 (12.62%)  13
Dyspepsia  1  9/103 (8.74%)  9
Nausea  1  28/103 (27.18%)  33
Vomiting  1  9/103 (8.74%)  9
General disorders   
Asthenia  1  6/103 (5.83%)  6
Fatigue  1  35/103 (33.98%)  56
Metabolism and nutrition disorders   
Decreased appetite  1  15/103 (14.56%)  16
Musculoskeletal and connective tissue disorders   
Arthralgia  1  12/103 (11.65%)  14
Back pain  1  14/103 (13.59%)  15
Pain in extremity  1  11/103 (10.68%)  11
Nervous system disorders   
Dizziness  1  14/103 (13.59%)  15
Dysgeusia  1  6/103 (5.83%)  7
Headache  1  14/103 (13.59%)  15
Restless legs syndrome  1  7/103 (6.80%)  7
Psychiatric disorders   
Anxiety  1  9/103 (8.74%)  12
Respiratory, thoracic and mediastinal disorders   
Cough  1  9/103 (8.74%)  9
Dyspnoea  1  14/103 (13.59%)  15
Epistaxis  1  9/103 (8.74%)  13
Skin and subcutaneous tissue disorders   
Pruritus  1  6/103 (5.83%)  6
Vascular disorders   
Hot flush  1  17/103 (16.50%)  18
Hypertension  1  6/103 (5.83%)  8
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
Name/Title: Clinical Trial Disclosure
Organization: Astellas Global Development, Inc. (APGD)
Phone: 800-888-7704 ext 5473
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT02091960     History of Changes
Other Study ID Numbers: 9785-CL-1121
2013-000093-29 ( EudraCT Number )
First Submitted: March 18, 2014
First Posted: March 19, 2014
Results First Submitted: February 27, 2018
Results First Posted: May 16, 2018
Last Update Posted: March 19, 2019