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A Phase 3 Comparative Study of TAP-144-SR(6M) in Postoperative and Hormone Therapy-naïve Patients With Premenopausal Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01546649
First received: February 28, 2012
Last updated: October 22, 2015
Last verified: October 2015
Results First Received: October 22, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Premenopausal Breast Cancer
Interventions: Drug: TAP-144-SR(6M)
Drug: TAP-144-SR(3M)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 21 investigative sites in Japan from April 2012 to December 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a historical diagnosis of premenopausal breast cancer were enrolled in 1 of 2 treatment groups as follows: TAP-144-SR(6M); TAP-144-SR(3M)

Reporting Groups
  Description
TAP-144-SR (6M) TAP-144-SR (6M) 22.5 milligram (mg), injection, subcutaneous, once in 24 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks.
TAP-144-SR (3M) TAP-144-SR (3M) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks.

Participant Flow:   Overall Study
    TAP-144-SR (6M)   TAP-144-SR (3M)
STARTED   83   84 
COMPLETED   75   75 
NOT COMPLETED   8   9 
Adverse Event                4                5 
Protocol Violation                1                0 
Lack of Efficacy                1                0 
Recurrence                1                1 
Discovery of secondary cancer                0                1 
Withdrawal by Subject                1                2 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS) included all randomized participants who had received at least a single dose of study treatment.

Reporting Groups
  Description
TAP-144-SR (6M) TAP-144-SR (6M) 22.5 milligram (mg), injection, subcutaneous, once in 24 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks.
TAP-144-SR (3M) TAP-144-SR (3M) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks.
Total Total of all reporting groups

Baseline Measures
   TAP-144-SR (6M)   TAP-144-SR (3M)   Total 
Overall Participants Analyzed 
[Units: Participants]
 83   84   167 
Age 
[Units: Years]
Mean (Standard Deviation)
 44.2  (4.90)   44.0  (5.18)   44.1  (5.03) 
Age, Customized 
[Units: Participants]
     
Less than (<) 40 years   13   12   25 
Greater than equal to (>=) 40 to <45 years   29   30   59 
>=45 years   41   42   83 
Gender 
[Units: Participants]
     
Female   83   84   167 
Male   0   0   0 
Height 
[Units: Centimeter (cm)]
Mean (Standard Deviation)
 159.3  (5.11)   158.1  (5.00)   158.7  (5.08) 
Height, Customized 
[Units: Participants]
     
<150 cm   2   3   5 
>=150 to <160 cm   40   53   93 
>=160 cm   41   28   69 
Weight 
[Units: Kilogram (kg)]
Mean (Standard Deviation)
 54.48  (7.670)   53.57  (7.498)   54.02  (7.574) 
Weight, Customized 
[Units: Participants]
     
<50 kg   25   29   54 
>=50 to <60 kg   40   40   80 
>=60 kg   18   15   33 
Body Mass Index (BMI) 
[Units: Kilogram per square meter (kg/m^2)]
Mean (Standard Deviation)
 21.50  (3.042)   21.45  (2.902)   21.48  (2.964) 
BMI, Customized 
[Units: Participants]
     
<18.5 kg/m^2   8   13   21 
>=18.5 to <25.0 kg/m^2   63   61   124 
>=25.0 to <30.0 kg/m^2   12   9   21 
>=30.0 kg/m^2   0   1   1 
Surgical procedure, Customized 
[Units: Participants]
     
Breast-conserving surgery   53   58   111 
Mastectomy   30   26   56 
Pathological diagnosis, Customized 
[Units: Participants]
     
Papillotubular carcinoma   33   36   69 
Solid-tubular carcinoma   7   4   11 
Scirrhous carcinoma   30   34   64 
Mucinous carcinoma   4   1   5 
Invasive lobular carcinoma   6   6   12 
Tubular adenocarcinoma   1   0   1 
Invasive micropapillary carcinoma   1   3   4 
Specified neoplasms (other)   1   0   1 
TNM classification: clinical tumor stage T, Customized [1] 
[Units: Participants]
     
T1   63   64   127 
T2   19   18   37 
T3   1   2   3 
[1] The frequency of clinical tumor stage T (0, 1, 2, 3, 4, X, or Tis) was assessed. The frequency of T was evaluated prior to surgery. The categories of T are ranged from 0 (No evidence of primary tumor) to 4 (Tumor of any size with direct extension to chest wall and/or to skin). X is representing tumor cannot be evaluated, 0 is representing no signs of tumor, Tis is carcinoma in situ.
TNM classification: regional lymph node stage N, Customized [1] 
[Units: Participants]
     
N0   78   81   159 
N1   5   3   8 
[1] The frequency of regional lymph nodes stage N (0, 1, 2, 3, or X) was assessed. The frequency of N was evaluated prior to surgery. The categories of N are ranged from 0 (No regional lymph node metastasis) to 3 (Metastasis in ipsilateral infraclavicular lymph node(s); or in clinically detected ipsilateral internal mammary lymph node(s); or metastasis in ipsilateral supraclavicular lymph node(s)). X is representing lymph nodes cannot be evaluated, 0 is tumor cells absent from regional lymph nodes.
TNM classification: M0 [1] 
[Units: Participants]
 83   84   167 
[1] The frequency of distant metastasis clinical stage M (0, 1) was assessed. The frequency of M was evaluated prior to surgery. The categories of M are represented by 0 (no distant metastasis) and 1 (distant metastasis).
TNM staging (Stage), Customized [1] 
[Units: Participants]
     
 61   61   122 
IIA   19   21   40 
IIB   2   2   4 
IIIA   1   0   1 
[1] The stage of cancer based on TNM classification: Stage 0 (Carcinoma in situ which is staged by Tis, N0, M0), Stage IA (T1, N0, M0), IB (T0/T1, N1, M0), IIA (T0/T1, N1, M0 or T2, N0, M0), IIB (T2, N1, M0 or T3, N0, M0), IIIA (T0/T1/T2, N2, M0 or T3, N1/N2, M0), IIIB (T4, N0/N1/N2, M0) and IIIC (Any T, N3, M0), Stage IV(Any T, Any N, M1).
Histopathological tumor size 
[Units: Cm]
Mean (Standard Deviation)
 1.64  (1.312)   1.55  (1.023)   1.59  (1.173) 
Histopathological tumor size, Customized 
[Units: Participants]
     
Less than equal to (<=) 2.0 cm   65   66   131 
>2.0 cm   18   18   36 
Axillary lymph node metastases 
[Units: Number of metastases]
Mean (Standard Deviation)
 0.2  (0.46)   0.2  (0.57)   0.2  (0.52) 
Axillary lymph node metastases, Customized 
[Units: Participants]
     
Present   15   14   29 
Absent   68   70   138 
Axillary lymph node metastases, Customized 
[Units: Participants]
     
 68   70   138 
>=1 metastasis to <=3 metastases   15   14   29 
>=4 metastases   0   0   0 
Time from surgery or previous postoperative adjuvant therapy to administration of study drug 
[Units: Participants]
     
<=28 days   6   9   15 
>=29 to <=56 days   42   43   85 
>=57 days   35   32   67 
Primary tumor estrogen receptors (ER)/ progesterone receptors (PgR) status, Customized 
[Units: Participants]
     
ER -positive / PgR-positive   82   82   164 
ER -positive / PgR -negative   1   2   3 
ER -negative / PgR -positive   0   0   0 
Human epidermal growth factor receptor 2 (HER2) (immunohistochemistry [IHC] scoring), Customized [1] 
[Units: Participants]
     
 37   33   70 
1+   33   28   61 
2+   7   13   20 
3+   0   0   0 
Not performed   6   10   16 
[1] Participants with HER expression by IHC was reported as 0, 1+, 2+, 3+, or unmeasured. The categories of HER expression is ranged from 0 (better) to 3+ (worse).
HER2 (fluorescent in situ hybridization [FISH] testing), Customized 
[Units: Participants]
     
Positive   0   0   0 
Negative   13   23   36 
Equivocal   0   0   0 
Not performed   70   61   131 
The eastern cooperative oncology group performance status (ECOG P.S.), Customized [1] 
[Units: Participants]
     
 83   84   167 
 0   0   0 
[1] Following are ECOG grades. 0: Fully active, perform all pre-disease activities without restriction. 1: Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of selfcare, unable to carry out any work activities, up and about more than (>) 50% of waking hours. 3: Capable of limited selfcare, confined to bed or chair >50% of waking hours. 4: Completely disabled, not capable of any selfcare, totally confined to bed or chair.
Menstruation (before the first dose), Customized 
[Units: Participants]
     
Present   82   81   163 
Absent   1   3   4 
Time from last menstruation to first dose 
[Units: Days]
Mean (Standard Deviation)
 17.0  (13.27)   15.9  (14.28)   16.4  (13.75) 
Time from last menstruation to first dose, Customized 
[Units: Participants]
     
<=28 days   72   73   145 
>=29 to <=56 days   8   6   14 
>=57 days   2   2   4 
Missing   1   3   4 
Serum Estradiol (E2) concentration (pretreatment) 
[Units: Picogram per milliliter (pg/mL)]
Mean (Standard Deviation)
 168.0  (162.99)   138.2  (125.45)   153.0  (145.66) 
Serum E2 concentration (pretreatment), Customized 
[Units: Participants]
     
<=29 pg/mL   7   11   18 
>=30 pg/mL   76   73   149 
Radiation, Customized [1] 
[Units: Participants]
     
Present   52   59   111 
Absent   31   25   56 
[1] Participants were classified based on whether they had received radiation therapy or not.
Preoperative and postoperative chemotherapy, Customized 
[Units: Participants]
     
Present   0   1   1 
Absent   83   83   166 
Previous breast cancer (other), Customized 
[Units: Participants]
     
Present   0   0   0 
Absent   83   84   167 
Concomitant osteoporosis medication , Customized 
[Units: Participants]
     
Present   6   9   15 
Absent   77   75   152 
Smoking Classification, Customized 
[Units: Participants]
     
Never Smoked   55   54   109 
Current Smoker   9   11   20 
Ex-smoker   19   19   38 
Time from surgery or previous postoperative adjuvant therapy to administration of study drug 
[Units: Days]
Mean (Standard Deviation)
 55.4  (21.69)   51.8  (16.01)   53.6  (19.08) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Suppressive Effect of Serum Estradiol (E2) to Menopausal Level (=<30 pg/mL) From Week 4 Through Week 48   [ Time Frame: Week 4 up to Week 48 ]

2.  Secondary:   Concentration of Serum E2   [ Time Frame: Baseline, Hour (hr) 1, 3, 6 on Day 1, Day 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, 169, 176, 183, 197, 225, 253, 281, 309, 337, 421, 505, 589 and 673 ]

3.  Secondary:   Concentration of Serum Luteinizing Hormone (LH)   [ Time Frame: Baseline, Hour 1, 3, 6 on Day 1, Day 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, 169, 176, 183, 197, 225, 253, 281, 309, 337, 421, 505, 589 and 673 ]

4.  Secondary:   Concentration of Follicle Stimulating Hormone (FSH)   [ Time Frame: Baseline, Hour 1, 3, 6 on Day 1, Day 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, 169, 176, 183, 197, 225, 253, 281, 309, 337, 421, 505, 589 and 673 ]

5.  Secondary:   Disease Free Survival (DFS) Rate at Week 96   [ Time Frame: Week 96 ]

6.  Secondary:   Distant Disease Free Survival (DDFS) Rate at Week 96   [ Time Frame: Week 96 ]

7.  Secondary:   Serum Unchanged TAP-144 Level   [ Time Frame: Baseline, Hour 1, 3, 6 on Day 1, Day 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, 169, 176, 183, 197, 225, 253, 281, 309 and 337 ]

8.  Secondary:   QT Interval Measured by 12-lead Electrocardiogram (ECG)   [ Time Frame: Baseline, Hour 1, 3, 6 on Day 1, Day 29, 85, 169 and 337 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director
Organization: Takeda
phone: +1-877-825-3327
e-mail: clinicaltrialregistry@tpna.com



Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01546649     History of Changes
Other Study ID Numbers: TAP-144-SR(6M)IP/CPH-202
JapicCTI-121762 ( Registry Identifier: JapicCTI )
U1111-1128-7039 ( Registry Identifier: WHO )
Study First Received: February 28, 2012
Results First Received: October 22, 2015
Last Updated: October 22, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare