A Phase 3 Comparative Study of TAP-144-SR(6M) in Postoperative and Hormone Therapy-naïve Patients With Premenopausal Breast Cancer
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT01546649
Collaborator
(none)
167
15
2
32
11.1
0.3
Study Details
Study Description
Brief Summary
Hormone dynamics, pharmacokinetics, safety, and efficacy of TAP-144-SR(6M) will be evaluated against TAP-144-SR(3M) in postoperative and hormone therapy-naïve patients with premenopausal breast cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
167 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Study Start Date
:
Apr 1, 2012
Actual Primary Completion Date
:
Dec 1, 2014
Actual Study Completion Date
:
Dec 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TAP-144-SR(6M) TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 96 weeks. |
Drug: TAP-144-SR(6M)
|
| Active Comparator: TAP-144-SR(3M) TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 96 weeks. |
Drug: TAP-144-SR(3M)
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Suppressive Effect of Serum Estradiol (E2) to Menopausal Level (=<30 pg/mL) From Week 4 Through Week 48 [Week 4 up to Week 48]
Comparison of both the treatment groups was done by assessing the suppressive effect on serum E2 concentration maintained at menopausal level (=<30pg/mL). Suppression rate was calculated as proportion of participants maintained at menopausal level.
Secondary Outcome Measures
- Concentration of Serum E2 [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]
The measure indicates serum E2 concentration at baseline and post-baseline time points.
- Concentration of Serum Luteinizing Hormone (LH) [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]
This measure indicates serum LH concentration at baseline and post-baseline time points. It was measured in milli-international units per milliliter (mIU/mL).
- Concentration of Follicle Stimulating Hormone (FSH) [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]
This measure indicates serum FSH concentration at baseline and post-baseline time points.
- Disease Free Survival (DFS) Rate at Week 96 [Week 96]
DFS is defined as time from randomization to earliest day of onset the events, recurrence [including recurrence in the ipsilateral breast], secondary cancer [including breast cancer in the contralateral breast] and death. DFS at Week 96 was defined as the percentage, calculated with Kaplan-Meier method, of participants did not experience any events at Week 96 since the randomization.
- Distant Disease Free Survival (DDFS) Rate at Week 96 [Week 96]
DDFS is defined as time from randomization to earliest day of onset the events, distant recurrence, secondary cancer [including breast cancer in the contralateral breast] and death. DDFS at week 96 was defined as the percentage calculated with Kaplan-Meier method, of participants did not experience any events at week 96 since the randomization.
- Serum Unchanged TAP-144 Level [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]
This measure indicates the unchanged TAP-144 level in serum.
- QT Interval Measured by 12-lead Electrocardiogram (ECG) [Baseline, Hour 1, 3, 6 on Day 1, Day 29, 85, 169 and 337]
12-lead electrocardiography measurement was performed in supine position after 5 minutes at rest. Each measurement was recorded continuously for 10 seconds at the recording speed of 25 millimeter/second (mm/second).
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
The participant has histopathologically-confirmed primary breast cancer in Japanese.
-
The participant is aged 20 years or older when informed consent is obtained
-
The participant has estrogen receptor (ER)-positive tumor cells and/or progesterone receptor (PgR)-positive primary tumor. And HER-2 is negative.
-
The participant has breast cancer in the clinical stages of T1-T3, N-any and M0 by TNM classification (the seventh edition, proposed by UICC in 2009). (No distant metastasis to lung, liver and bone should be confirmed on the image-based diagnosis at study enrollment. The image taken within 12 weeks prior to study enrollment is also available for the diagnosis.) The number of axillary lymph node metastasis is not limited.
-
Any operative procedure for breast cancer is acceptable. In principle, after breast-conserving surgery, the participant will receive postoperative radiation to the conserving breast.
-
Neoadjuvant chemotherapy and adjuvant chemotherapy prior to study enrollment are acceptable. (It is advisable the same kind of chemotherapy is performed at each site.)
-
The participant has a history of regular menstrual periods within 12 weeks prior to study enrollment, or the participant has FSH of less than 40 mIU/mL and E2 of 10 pg/mL or more measured within 12 weeks prior to study enrollment. The participant has not had a chemical menopause (i.e., FSH of less than 40 mIU/mL and E2 of 10 pg/mL or more) within 12 weeks after completing adjuvant chemotherapy.
-
The participant is in a condition to receive study drug and Tamoxifen (TAM) within 12 weeks after surgery or after adjuvant chemotherapy prior to study enrollment. Adjuvant chemotherapy prior to study is required to have been completed at the time of study enrollment.
-
The participant has ECOG performance status of grades 0 or 1 at the time of study enrollment.
-
The participant meets the following criteria of hepatic, renal and bone marrow functions on the laboratory test results at screening:
-
Hepatic function: AST (GOT) ≤ 3.0 times the upper limit of normal (ULN) ALT (GPT) ≤ 3.0 times the ULN
-
Renal function: serum creatinine level < 1.5 times the ULN
-
Bone marrow function : white blood cell count ≥ 3,000/mm3 platelet count ≥ 100,000/μL hemoglobin ≥ 10.0g/dL
- The participant agrees to use a non-hormonal method of contraception through the study period.
Exclusion Criteria:
-
The participant has received neoadjuvant or adjuvant hormonal therapy for the latest breast cancer surgery.
-
The participant has received bilateral oophorectomy and bilateral ovarian irradiation.
-
The participant has inflammatory breast cancer or bilateral breast cancer.
-
The participant has non-invasive ductal carcinoma.
-
The participant has multiple primary cancers, or a history of carcinoma in other organs.
-
The participant is pregnant or breast-feeding.
-
The participant has a history of hypersensitivity to synthetic LH-RH, LH-RH derivative, TAM, TAM analogue (antiestrogen) or any component of the study drug.
-
The participant has a history of, or has been diagnosed with thromboembolism including myocardial infarction, cerebral infarction, venous thrombosis, and pulmonary embolism, or cardiac failure.
-
Patients whose QTcF interval exceeded 460 msec on the 12-lead electrocardiogram at screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nagoya-shi | Aichi | Japan | ||
| 2 | Fukushima-shi | Fukushima | Japan | ||
| 3 | Maebashi-shi | Gunma | Japan | ||
| 4 | Ohta-shi | Gunma | Japan | ||
| 5 | Sapporo-shi | Hokkaido | Japan | ||
| 6 | Isehara-shi | Kanagawa | Japan | ||
| 7 | Yokohama-shi | Kanagawa | Japan | ||
| 8 | Kumamoto-shi | Kumamoto | Japan | ||
| 9 | Kyoto-shi | Kyoto | Japan | ||
| 10 | Nigata-shi | Nigata | Japan | ||
| 11 | Kurashiki-shi | Okayama | Japan | ||
| 12 | Osaka-shi | Osaka | Japan | ||
| 13 | Suita-shi | Osaka | Japan | ||
| 14 | Kita-adachi-gun | Saitama | Japan | ||
| 15 | Shinjuku-ku | Tokyo | Japan |
Sponsors and Collaborators
- Takeda
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT01546649
Other Study ID Numbers:
- TAP-144-SR(6M)IP/CPH-202
- JapicCTI-121762
- U1111-1128-7039
First Posted:
Mar 7, 2012
Last Update Posted:
Nov 26, 2015
Last Verified:
Oct 1, 2015
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 21 investigative sites in Japan from April 2012 to December 2014. |
|---|---|
| Pre-assignment Detail | 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) |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Period Title: Overall Study | ||
| STARTED | 83 | 84 |
| COMPLETED | 75 | 75 |
| NOT COMPLETED | 8 | 9 |
Baseline Characteristics
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) | Total |
|---|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. | Total of all reporting groups |
| Overall Participants | 83 | 84 | 167 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
44.2
(4.90)
|
44.0
(5.18)
|
44.1
(5.03)
|
| Age, Customized (participants) [Number] | |||
| Less than (<) 40 years |
13
15.7%
|
12
14.3%
|
25
15%
|
| Greater than equal to (>=) 40 to <45 years |
29
34.9%
|
30
35.7%
|
59
35.3%
|
| >=45 years |
41
49.4%
|
42
50%
|
83
49.7%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
83
100%
|
84
100%
|
167
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Height (centimeter (cm)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [centimeter (cm)] |
159.3
(5.11)
|
158.1
(5.00)
|
158.7
(5.08)
|
| Height, Customized (participants) [Number] | |||
| <150 cm |
2
2.4%
|
3
3.6%
|
5
3%
|
| >=150 to <160 cm |
40
48.2%
|
53
63.1%
|
93
55.7%
|
| >=160 cm |
41
49.4%
|
28
33.3%
|
69
41.3%
|
| Weight (kilogram (kg)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilogram (kg)] |
54.48
(7.670)
|
53.57
(7.498)
|
54.02
(7.574)
|
| Weight, Customized (participants) [Number] | |||
| <50 kg |
25
30.1%
|
29
34.5%
|
54
32.3%
|
| >=50 to <60 kg |
40
48.2%
|
40
47.6%
|
80
47.9%
|
| >=60 kg |
18
21.7%
|
15
17.9%
|
33
19.8%
|
| Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
21.50
(3.042)
|
21.45
(2.902)
|
21.48
(2.964)
|
| BMI, Customized (participants) [Number] | |||
| <18.5 kg/m^2 |
8
9.6%
|
13
15.5%
|
21
12.6%
|
| >=18.5 to <25.0 kg/m^2 |
63
75.9%
|
61
72.6%
|
124
74.3%
|
| >=25.0 to <30.0 kg/m^2 |
12
14.5%
|
9
10.7%
|
21
12.6%
|
| >=30.0 kg/m^2 |
0
0%
|
1
1.2%
|
1
0.6%
|
| Surgical procedure, Customized (participants) [Number] | |||
| Breast-conserving surgery |
53
63.9%
|
58
69%
|
111
66.5%
|
| Mastectomy |
30
36.1%
|
26
31%
|
56
33.5%
|
| Pathological diagnosis, Customized (participants) [Number] | |||
| Papillotubular carcinoma |
33
39.8%
|
36
42.9%
|
69
41.3%
|
| Solid-tubular carcinoma |
7
8.4%
|
4
4.8%
|
11
6.6%
|
| Scirrhous carcinoma |
30
36.1%
|
34
40.5%
|
64
38.3%
|
| Mucinous carcinoma |
4
4.8%
|
1
1.2%
|
5
3%
|
| Invasive lobular carcinoma |
6
7.2%
|
6
7.1%
|
12
7.2%
|
| Tubular adenocarcinoma |
1
1.2%
|
0
0%
|
1
0.6%
|
| Invasive micropapillary carcinoma |
1
1.2%
|
3
3.6%
|
4
2.4%
|
| Specified neoplasms (other) |
1
1.2%
|
0
0%
|
1
0.6%
|
| TNM classification: clinical tumor stage T, Customized (participants) [Number] | |||
| T1 |
63
75.9%
|
64
76.2%
|
127
76%
|
| T2 |
19
22.9%
|
18
21.4%
|
37
22.2%
|
| T3 |
1
1.2%
|
2
2.4%
|
3
1.8%
|
| TNM classification: regional lymph node stage N, Customized (participants) [Number] | |||
| N0 |
78
94%
|
81
96.4%
|
159
95.2%
|
| N1 |
5
6%
|
3
3.6%
|
8
4.8%
|
| TNM classification: M0 (participants) [Number] | |||
| Number [participants] |
83
100%
|
84
100%
|
167
100%
|
| TNM staging (Stage), Customized (participants) [Number] | |||
| I |
61
73.5%
|
61
72.6%
|
122
73.1%
|
| IIA |
19
22.9%
|
21
25%
|
40
24%
|
| IIB |
2
2.4%
|
2
2.4%
|
4
2.4%
|
| IIIA |
1
1.2%
|
0
0%
|
1
0.6%
|
| Histopathological tumor size (cm) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [cm] |
1.64
(1.312)
|
1.55
(1.023)
|
1.59
(1.173)
|
| Histopathological tumor size, Customized (participants) [Number] | |||
| Less than equal to (<=) 2.0 cm |
65
78.3%
|
66
78.6%
|
131
78.4%
|
| >2.0 cm |
18
21.7%
|
18
21.4%
|
36
21.6%
|
| Axillary lymph node metastases (number of metastases) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [number of metastases] |
0.2
(0.46)
|
0.2
(0.57)
|
0.2
(0.52)
|
| Axillary lymph node metastases, Customized (participants) [Number] | |||
| Present |
15
18.1%
|
14
16.7%
|
29
17.4%
|
| Absent |
68
81.9%
|
70
83.3%
|
138
82.6%
|
| Axillary lymph node metastases, Customized (participants) [Number] | |||
| 0 |
68
81.9%
|
70
83.3%
|
138
82.6%
|
| >=1 metastasis to <=3 metastases |
15
18.1%
|
14
16.7%
|
29
17.4%
|
| >=4 metastases |
0
0%
|
0
0%
|
0
0%
|
| Time from surgery or previous postoperative adjuvant therapy to administration of study drug (participants) [Number] | |||
| <=28 days |
6
7.2%
|
9
10.7%
|
15
9%
|
| >=29 to <=56 days |
42
50.6%
|
43
51.2%
|
85
50.9%
|
| >=57 days |
35
42.2%
|
32
38.1%
|
67
40.1%
|
| Primary tumor estrogen receptors (ER)/ progesterone receptors (PgR) status, Customized (participants) [Number] | |||
| ER -positive / PgR-positive |
82
98.8%
|
82
97.6%
|
164
98.2%
|
| ER -positive / PgR -negative |
1
1.2%
|
2
2.4%
|
3
1.8%
|
| ER -negative / PgR -positive |
0
0%
|
0
0%
|
0
0%
|
| Human epidermal growth factor receptor 2 (HER2) (immunohistochemistry [IHC] scoring), Customized (participants) [Number] | |||
| 0 |
37
44.6%
|
33
39.3%
|
70
41.9%
|
| 1+ |
33
39.8%
|
28
33.3%
|
61
36.5%
|
| 2+ |
7
8.4%
|
13
15.5%
|
20
12%
|
| 3+ |
0
0%
|
0
0%
|
0
0%
|
| Not performed |
6
7.2%
|
10
11.9%
|
16
9.6%
|
| HER2 (fluorescent in situ hybridization [FISH] testing), Customized (participants) [Number] | |||
| Positive |
0
0%
|
0
0%
|
0
0%
|
| Negative |
13
15.7%
|
23
27.4%
|
36
21.6%
|
| Equivocal |
0
0%
|
0
0%
|
0
0%
|
| Not performed |
70
84.3%
|
61
72.6%
|
131
78.4%
|
| The eastern cooperative oncology group performance status (ECOG P.S.), Customized (participants) [Number] | |||
| 0 |
83
100%
|
84
100%
|
167
100%
|
| 1 |
0
0%
|
0
0%
|
0
0%
|
| Menstruation (before the first dose), Customized (participants) [Number] | |||
| Present |
82
98.8%
|
81
96.4%
|
163
97.6%
|
| Absent |
1
1.2%
|
3
3.6%
|
4
2.4%
|
| Time from last menstruation to first dose (days) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [days] |
17.0
(13.27)
|
15.9
(14.28)
|
16.4
(13.75)
|
| Time from last menstruation to first dose, Customized (participants) [Number] | |||
| <=28 days |
72
86.7%
|
73
86.9%
|
145
86.8%
|
| >=29 to <=56 days |
8
9.6%
|
6
7.1%
|
14
8.4%
|
| >=57 days |
2
2.4%
|
2
2.4%
|
4
2.4%
|
| Missing |
1
1.2%
|
3
3.6%
|
4
2.4%
|
| Serum Estradiol (E2) concentration (pretreatment) (picogram per milliliter (pg/mL)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [picogram per milliliter (pg/mL)] |
168.0
(162.99)
|
138.2
(125.45)
|
153.0
(145.66)
|
| Serum E2 concentration (pretreatment), Customized (participants) [Number] | |||
| <=29 pg/mL |
7
8.4%
|
11
13.1%
|
18
10.8%
|
| >=30 pg/mL |
76
91.6%
|
73
86.9%
|
149
89.2%
|
| Radiation, Customized (participants) [Number] | |||
| Present |
52
62.7%
|
59
70.2%
|
111
66.5%
|
| Absent |
31
37.3%
|
25
29.8%
|
56
33.5%
|
| Preoperative and postoperative chemotherapy, Customized (participants) [Number] | |||
| Present |
0
0%
|
1
1.2%
|
1
0.6%
|
| Absent |
83
100%
|
83
98.8%
|
166
99.4%
|
| Previous breast cancer (other), Customized (participants) [Number] | |||
| Present |
0
0%
|
0
0%
|
0
0%
|
| Absent |
83
100%
|
84
100%
|
167
100%
|
| Concomitant osteoporosis medication , Customized (participants) [Number] | |||
| Present |
6
7.2%
|
9
10.7%
|
15
9%
|
| Absent |
77
92.8%
|
75
89.3%
|
152
91%
|
| Smoking Classification, Customized (participants) [Number] | |||
| Never Smoked |
55
66.3%
|
54
64.3%
|
109
65.3%
|
| Current Smoker |
9
10.8%
|
11
13.1%
|
20
12%
|
| Ex-smoker |
19
22.9%
|
19
22.6%
|
38
22.8%
|
| Time from surgery or previous postoperative adjuvant therapy to administration of study drug (days) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [days] |
55.4
(21.69)
|
51.8
(16.01)
|
53.6
(19.08)
|
Outcome Measures
| Title | Percentage of Participants With Suppressive Effect of Serum Estradiol (E2) to Menopausal Level (=<30 pg/mL) From Week 4 Through Week 48 |
|---|---|
| Description | Comparison of both the treatment groups was done by assessing the suppressive effect on serum E2 concentration maintained at menopausal level (=<30pg/mL). Suppression rate was calculated as proportion of participants maintained at menopausal level. |
| Time Frame | Week 4 up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomized participants who had received at least a single dose of study treatment. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Number (95% Confidence Interval) [percentage of participants] |
97.6
117.6%
|
96.4
114.8%
|
| Title | Concentration of Serum E2 |
|---|---|
| Description | The measure indicates serum E2 concentration at baseline and post-baseline time points. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomized participants who had received at least a single dose of study treatment. Here 'N' represents evaluable baseline and post-baseline assessment population. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Baseline [N=83;84] |
95
|
99
|
| Day1 (1hr) [N=82;84] |
94.5
|
110.5
|
| Day1 (3hr) [N=24;21] |
102.0
|
64.0
|
| Day1 (6hr) [N=24;21] |
153.5
|
99.0
|
| Day2 [N=83;84] |
146.0
|
115.5
|
| Day3 [N=83;84] |
100.0
|
87.5
|
| Day4 [N=83;84] |
108.0
|
110.0
|
| Week 1 (Day8) [N=83;84] |
56.0
|
112.0
|
| Week 2 (Day15) [N=83;84] |
13.0
|
0.0
|
| Week 3 (Day22) [N=83;84] |
0.0
|
0.0
|
| Week 4 (Day29) [N=83;84] |
0.0
|
0.0
|
| Week 8 (Day57) [N=83;84] |
0.0
|
0.0
|
| Week 12 (Day85) [N=83;83] |
0.0
|
0.0
|
| Week 16 (Day113) [N=82;82] |
0.0
|
0.0
|
| Week 20 (Day141) [N=81;82] |
0.0
|
0.0
|
| Week 24 (Day169) [N=80;81] |
0.0
|
0.0
|
| Week 25 (Day176) [N=79;80] |
0.0
|
0.0
|
| Week 26 (Day183) [N=79;80] |
0.0
|
0.0
|
| Week 28 (Day197) [N=75;77] |
0.0
|
0.0
|
| Week 32 (Day225) [N=78;80] |
0.0
|
0.0
|
| Week 36 (Day253) [N=79;80] |
0.0
|
0.0
|
| Week 40 (Day281) [N=78;80] |
0.0
|
0.0
|
| Week 44 (Day309) [N=77;80] |
0.0
|
0.0
|
| Week 48 (Day337) [N=77;80] |
0.0
|
0.0
|
| Week 60 (Day421) [N=77;79] |
0.0
|
0.0
|
| Week 72 (Day505) [N=77;78] |
0.0
|
0.0
|
| Week 84 (Day589) [N=76;77] |
0.0
|
0.0
|
| Week 96 (Day673) [N=75;75] |
0.0
|
0.0
|
| Title | Concentration of Serum Luteinizing Hormone (LH) |
|---|---|
| Description | This measure indicates serum LH concentration at baseline and post-baseline time points. It was measured in milli-international units per milliliter (mIU/mL). |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomized participants who had received at least a single dose of study treatment. Here 'N' represents evaluable baseline and post-baseline assessment population. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Baseline [N=83;84] |
4.250
|
4.490
|
| Day1 (1hr) [N=82;84] |
27.730
|
30.585
|
| Day1 (3hr) [N=24;21] |
88.020
|
63.260
|
| Day1 (6hr) [N=24;21] |
64.750
|
61.210
|
| Day2 [N=83;84] |
14.990
|
19.755
|
| Day3 [N=83;84] |
7.310
|
10.500
|
| Day4 [N=83;84] |
5.830
|
9.375
|
| Week 1 (Day8) [N=83;84] |
3.190
|
4.475
|
| Week 2 (Day15) [N=83;84] |
2.460
|
1.990
|
| Week 3 (Day22) [N=83;84] |
1.020
|
1.085
|
| Week 4 (Day29) [N=83;84] |
0.540
|
0.845
|
| Week 8 (Day57) [N=83;84] |
0.270
|
0.570
|
| Week 12 (Day85) [N=83;83] |
0.220
|
0.520
|
| Week 16 (Day113) [N=82;82] |
0.245
|
0.430
|
| Week 20 (Day141) [N=81;82] |
0.240
|
0.405
|
| Week 24 (Day169) [N=80;81] |
0.290
|
0.460
|
| Week 25 (Day176) [N=79;80] |
0.450
|
0.455
|
| Week 26 (Day183) [N=79;80] |
0.410
|
0.405
|
| Week 28 (Day197) [N=75;77] |
0.270
|
0.410
|
| Week 32 (Day225) [N=78;80] |
0.280
|
0.440
|
| Week 36 (Day253) [N=79;80] |
0.250
|
0.395
|
| Week 40 (Day281) [N=78;80] |
0.240
|
0.390
|
| Week 44 (Day309) [N=77;80] |
0.250
|
0.385
|
| Week 48 (Day337) [N=77;80] |
0.250
|
0.415
|
| Week 60 (Day421) [N=77;79] |
0.250
|
0.440
|
| Week 72 (Day505) [N=77;78] |
0.260
|
0.420
|
| Week 84 (Day589) [N=76;77] |
0.230
|
0.410
|
| Week 96 (Day673) [N=75;75] |
0.210
|
0.360
|
| Title | Concentration of Follicle Stimulating Hormone (FSH) |
|---|---|
| Description | This measure indicates serum FSH concentration at baseline and post-baseline time points. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomized participants who had received at least a single dose of study treatment. Here 'N' represents evaluable baseline and post-baseline assessment population. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Baseline [N=83;84] |
5.070
|
5.605
|
| Day1 (1hr) [N=82;84] |
9.520
|
10.000
|
| Day1 (3hr) [N=24;21] |
23.325
|
19.950
|
| Day1 (6hr) [N=24;21] |
27.460
|
25.340
|
| Day2 [N=83;84] |
10.080
|
12.515
|
| Day3 [N=83;84] |
6.180
|
6.780
|
| Day4 [N=83;84] |
6.100
|
5.585
|
| Week 1 (Day8) [N=83;84] |
3.920
|
3.035
|
| Week 2 (Day15) [N=83;84] |
1.820
|
1.705
|
| Week 3 (Day22) [N=83;84] |
1.220
|
1.570
|
| Week 4 (Day29) [N=83;84] |
1.200
|
2.015
|
| Week 8 (Day57) [N=83;84] |
1.390
|
2.345
|
| Week 12 (Day85) [N=83;83] |
1.490
|
2.240
|
| Week 16 (Day113) [N=82;82] |
1.635
|
1.830
|
| Week 20 (Day141) [N=81;82] |
1.780
|
1.905
|
| Week 24 (Day169) [N=80;81] |
2.060
|
2.000
|
| Week 25 (Day176) [N=79;80] |
1.940
|
1.600
|
| Week 26 (Day183) [N=79;80] |
1.560
|
1.700
|
| Week 28 (Day197) [N=75;77] |
1.310
|
1.690
|
| Week 32 (Day225) [N=78;80] |
1.595
|
1.980
|
| Week 36 (Day253) [N=79;80] |
1.660
|
2.035
|
| Week 40 (Day281) [N=78;80] |
1.735
|
1.710
|
| Week 44 (Day309) [N=77;80] |
1.930
|
1.825
|
| Week 48 (Day337) [N=77;80] |
1.920
|
1.885
|
| Week 60 (Day421) [N=77;79] |
1.530
|
1.910
|
| Week 72 (Day505) [N=77;78] |
1.730
|
1.920
|
| Week 84 (Day589) [N=76;77] |
1.500
|
1.840
|
| Week 96 (Day673) [N=75;75] |
1.620
|
1.740
|
| Title | Disease Free Survival (DFS) Rate at Week 96 |
|---|---|
| Description | DFS is defined as time from randomization to earliest day of onset the events, recurrence [including recurrence in the ipsilateral breast], secondary cancer [including breast cancer in the contralateral breast] and death. DFS at Week 96 was defined as the percentage, calculated with Kaplan-Meier method, of participants did not experience any events at Week 96 since the randomization. |
| Time Frame | Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomized participants who had received at least a single dose of study treatment. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Number [percentage of participants] |
97.3
117.2%
|
97.5
116.1%
|
| Title | Distant Disease Free Survival (DDFS) Rate at Week 96 |
|---|---|
| Description | DDFS is defined as time from randomization to earliest day of onset the events, distant recurrence, secondary cancer [including breast cancer in the contralateral breast] and death. DDFS at week 96 was defined as the percentage calculated with Kaplan-Meier method, of participants did not experience any events at week 96 since the randomization. |
| Time Frame | Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomized participants who had received at least a single dose of study treatment. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Number [percentage of participants] |
98.5
118.7%
|
98.8
117.6%
|
| Title | Serum Unchanged TAP-144 Level |
|---|---|
| Description | This measure indicates the unchanged TAP-144 level in serum. |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all randomized participants who had received at least a single dose of study treatment. Here 'N' represents evaluable baseline and post-baseline assessment population. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Baseline [N=83;84] |
0.000
(0.0000)
|
0.000
(0.0000)
|
| Day1 (1hr) [N=82;84] |
5.293
(1.0684)
|
28.45
(9.7398)
|
| Day1 (3hr) [N=24;19] |
2.538
(0.46023)
|
20.27
(3.9535)
|
| Day1 (6hr) [N=24;21] |
1.039
(0.23264)
|
8.037
(1.7408)
|
| Day2 [N=83;84] |
0.1401
(0.066137)
|
0.4749
(0.17801)
|
| Day3 [N=83;84] |
0.02889
(0.026108)
|
0.2492
(0.097054)
|
| Day4 [N=83;84] |
0.02380
(0.022645)
|
0.2273
(0.080794)
|
| Week 1 (Day8) [N=82;83] |
0.09115
(0.22637)
|
0.1050
(0.049062)
|
| Week 2 (Day15) [N=82;84] |
0.3702
(0.25134)
|
0.08867
(0.077142)
|
| Week 3 (Day22) [N=83;84] |
0.7285
(0.35639)
|
0.06471
(0.092279)
|
| Week 4 (Day29) [N=83;83] |
0.3442
(0.19814)
|
0.04971
(0.032917)
|
| Week 8 (Day57) [N=83;83] |
0.1146
(0.053068)
|
0.04744
(0.032379)
|
| Week 12 (Day85) [N=83;83] |
0.08051
(0.041881)
|
0.06028
(0.031104)
|
| Week 16 (Day113) [N=82;82] |
0.05775
(0.037098)
|
0.09347
(0.077284)
|
| Week 20 (Day141) [N=81;82] |
0.03941
(0.037082)
|
0.07165
(0.062739)
|
| Week 24 (Day169) [N=80;81] |
0.02931
(0.019785)
|
0.07634
(0.064118)
|
| Week 25 (Day176) [N=79;80] |
0.1128
(0.16751)
|
0.1583
(0.089299)
|
| Week 26 (Day183) [N=79;80] |
0.3327
(0.36474)
|
0.1109
(0.065133)
|
| Week 28 (Day197) [N=80;80] |
0.4687
(0.36083)
|
0.08468
(0.040820)
|
| Week 32 (Day225) [N=78;80] |
0.1377
(0.093340)
|
0.06881
(0.037607)
|
| Week 36 (Day253) [N=79;80] |
0.08521
(0.040324)
|
0.06259
(0.036687)
|
| Week 40 (Day281) [N=79;80] |
0.06073
(0.032232)
|
0.08163
(0.031631)
|
| Week 44 (Day309) [N=77;80] |
0.4339
(0.026552)
|
0.06479
(0.028540)
|
| Week 48 (Day337) [N=77;80] |
0.02957
(0.017147)
|
0.06313
(0.032149)
|
| Title | QT Interval Measured by 12-lead Electrocardiogram (ECG) |
|---|---|
| Description | 12-lead electrocardiography measurement was performed in supine position after 5 minutes at rest. Each measurement was recorded continuously for 10 seconds at the recording speed of 25 millimeter/second (mm/second). |
| Time Frame | Baseline, Hour 1, 3, 6 on Day 1, Day 29, 85, 169 and 337 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety evaluation was conducted in the safety analysis set (SAS). Here 'N' represents evaluable baseline and post-baseline assessment population. |
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) |
|---|---|---|
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. |
| Measure Participants | 83 | 84 |
| Baseline [N=83;84] |
421.5
(16.05)
|
420.9
(16.53)
|
| Day1 (1hr) [N=83;84] |
417.8
(15.37)
|
417.1
(17.83)
|
| Day1 (3hr) [N=24;21] |
416.8
(11.34)
|
423.7
(18.90)
|
| Day1 (6hr) [N=24;21] |
415.8
(18.68)
|
424.1
(13.76)
|
| Week 4 (Day29) [N=83;84] |
431.2
(19.30)
|
432.3
(16.90)
|
| Week 12 (Day85) [N=83;84] |
433.3
(19.44)
|
432.3
(20.01)
|
| Week 24 (Day169) [N=81;82] |
431.0
(21.22)
|
429.0
(20.28)
|
| Week 48 (Day337) [N=77;80] |
430.0
(17.31)
|
431.4
(18.89)
|
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||
| Arm/Group Title | TAP-144-SR (6M) | TAP-144-SR (3M) | ||
| Arm/Group Description | 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) 11.25 mg, injection, subcutaneous, once in 12 weeks along with tamoxifen 20 mg, tablet, orally, once daily for up to 96 weeks. | ||
All Cause Mortality |
||||
| TAP-144-SR (6M) | TAP-144-SR (3M) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| TAP-144-SR (6M) | TAP-144-SR (3M) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/83 (7.2%) | 7/84 (8.3%) | ||
| Eye disorders | ||||
| Eyelid ptosis | 1/83 (1.2%) | 0/84 (0%) | ||
| Gastrointestinal disorders | ||||
| Anal fistula | 1/83 (1.2%) | 0/84 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 0/83 (0%) | 1/84 (1.2%) | ||
| Infections and infestations | ||||
| Gastroenteritis | 1/83 (1.2%) | 0/84 (0%) | ||
| Infectious mononucleosis | 1/83 (1.2%) | 0/84 (0%) | ||
| Sinusitis | 0/83 (0%) | 1/84 (1.2%) | ||
| Investigations | ||||
| Occult blood positive | 0/83 (0%) | 1/84 (1.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Intervertebral disc protrusion | 0/83 (0%) | 1/84 (1.2%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cervix carcinoma stage 0 | 0/83 (0%) | 1/84 (1.2%) | ||
| Nervous system disorders | ||||
| Multiple sclerosis | 1/83 (1.2%) | 0/84 (0%) | ||
| VIIth nerve paralysis | 1/83 (1.2%) | 0/84 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Interstitial lung disease | 1/83 (1.2%) | 1/84 (1.2%) | ||
| Pneumothorax | 0/83 (0%) | 1/84 (1.2%) | ||
| Vascular disorders | ||||
| Behcet's syndrome | 0/83 (0%) | 1/84 (1.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| TAP-144-SR (6M) | TAP-144-SR (3M) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 82/83 (98.8%) | 82/84 (97.6%) | ||
| Cardiac disorders | ||||
| Palpitations | 7/83 (8.4%) | 3/84 (3.6%) | ||
| Eye disorders | ||||
| Conjunctivitis | 5/83 (6%) | 3/84 (3.6%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 7/83 (8.4%) | 9/84 (10.7%) | ||
| Constipation | 13/83 (15.7%) | 2/84 (2.4%) | ||
| Vomiting | 6/83 (7.2%) | 4/84 (4.8%) | ||
| Gastritis | 6/83 (7.2%) | 3/84 (3.6%) | ||
| Diarrhoea | 5/83 (6%) | 2/84 (2.4%) | ||
| Toothache | 0/83 (0%) | 7/84 (8.3%) | ||
| General disorders | ||||
| Injection site induration | 36/83 (43.4%) | 33/84 (39.3%) | ||
| Injection site pain | 24/83 (28.9%) | 26/84 (31%) | ||
| Malaise | 13/83 (15.7%) | 13/84 (15.5%) | ||
| Injection site erythema | 13/83 (15.7%) | 8/84 (9.5%) | ||
| Injection site swelling | 12/83 (14.5%) | 5/84 (6%) | ||
| Injection site bruising | 5/83 (6%) | 7/84 (8.3%) | ||
| Pyrexia | 4/83 (4.8%) | 5/84 (6%) | ||
| Hepatobiliary disorders | ||||
| Hepatic steatosis | 6/83 (7.2%) | 8/84 (9.5%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 47/83 (56.6%) | 42/84 (50%) | ||
| Influenza | 8/83 (9.6%) | 4/84 (4.8%) | ||
| Cystitis | 5/83 (6%) | 3/84 (3.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Radiation skin injury | 31/83 (37.3%) | 39/84 (46.4%) | ||
| Radiation pneumonitis | 7/83 (8.4%) | 3/84 (3.6%) | ||
| Procedural pain | 3/83 (3.6%) | 6/84 (7.1%) | ||
| Wound complication | 2/83 (2.4%) | 5/84 (6%) | ||
| Investigations | ||||
| White blood cell count decreased | 27/83 (32.5%) | 19/84 (22.6%) | ||
| Weight increased | 12/83 (14.5%) | 8/84 (9.5%) | ||
| Gamma-glutamyltransferase increased | 3/83 (3.6%) | 12/84 (14.3%) | ||
| Electrocardiogram QT prolonged | 7/83 (8.4%) | 4/84 (4.8%) | ||
| Blood creatine phosphokinase increased | 5/83 (6%) | 3/84 (3.6%) | ||
| Bone density decreased | 3/83 (3.6%) | 5/84 (6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 18/83 (21.7%) | 20/84 (23.8%) | ||
| Musculoskeletal stiffness | 11/83 (13.3%) | 9/84 (10.7%) | ||
| Back pain | 13/83 (15.7%) | 6/84 (7.1%) | ||
| Osteoporosis | 5/83 (6%) | 3/84 (3.6%) | ||
| Nervous system disorders | ||||
| Headache | 21/83 (25.3%) | 19/84 (22.6%) | ||
| Dizziness | 6/83 (7.2%) | 9/84 (10.7%) | ||
| Somnolence | 0/83 (0%) | 6/84 (7.1%) | ||
| Psychiatric disorders | ||||
| Insomnia | 10/83 (12%) | 9/84 (10.7%) | ||
| Reproductive system and breast disorders | ||||
| Menopausal symptoms | 5/83 (6%) | 6/84 (7.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/83 (6%) | 6/84 (7.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis | 9/83 (10.8%) | 7/84 (8.3%) | ||
| Rash | 9/83 (10.8%) | 6/84 (7.1%) | ||
| Eczema | 3/83 (3.6%) | 9/84 (10.7%) | ||
| Vascular disorders | ||||
| Hot flush | 43/83 (51.8%) | 48/84 (57.1%) | ||
| Hypertension | 5/83 (6%) | 4/84 (4.8%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| clinicaltrialregistry@tpna.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT01546649
Other Study ID Numbers:
- TAP-144-SR(6M)IP/CPH-202
- JapicCTI-121762
- U1111-1128-7039
First Posted:
Mar 7, 2012
Last Update Posted:
Nov 26, 2015
Last Verified:
Oct 1, 2015