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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  
Number of Participants  
[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  
TNM classification: regional lymph node stage N, Customized [2]
[units: participants]
     
N0     78     81     159  
N1     5     3     8  
TNM classification: M0 [3]
[units: participants]
  83     84     167  
TNM staging (Stage), Customized [4]
[units: participants]
     
I     61     61     122  
IIA     19     21     40  
IIB     2     2     4  
IIIA     1     0     1  
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]
     
0     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 [5]
[units: participants]
     
0     37     33     70  
1+     33     28     61  
2+     7     13     20  
3+     0     0     0  
Not performed     6     10     16  
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 [6]
[units: participants]
     
0     83     84     167  
1     0     0     0  
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 [7]
[units: participants]
     
Present     52     59     111  
Absent     31     25     56  
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)  
[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.
[2] 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.
[3] 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).
[4] 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).
[5] 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).
[6] 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.
[7] Participants were classified based on whether they had received radiation therapy or not.



  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