Trial Outcomes & Findings for Adj TC + Herceptin Early Stage Breast Cancer (NCT NCT00493649)
NCT ID: NCT00493649
Last Updated: 2016-11-03
Results Overview
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
493 participants
Primary outcome timeframe
2 years
Results posted on
2016-11-03
Participant Flow
Participant milestones
| Measure |
TC+H
This is a nonrandomized, noncomparative, open-label Phase II study. On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive docetaxel (Taxotere) 75 mg/m\^2 IV plus cyclophosphamide (Cytoxan) 600 mg/m\^2 IV, plus weekly trastuzumab (Herceptin) 4 mg/kg IV (loading dose, Day 1, Cycle 1 only) and 2 mg/kg IV (on Days 1, 8, and 15) thereafter. Subsequent cycles of therapy will continue until a total of 4 cycles of TC+H have been completed. Then, patients will continue to receive trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care.
|
|---|---|
|
Overall Study
STARTED
|
493
|
|
Overall Study
COMPLETED
|
411
|
|
Overall Study
NOT COMPLETED
|
82
|
Reasons for withdrawal
| Measure |
TC+H
This is a nonrandomized, noncomparative, open-label Phase II study. On Day 1 of each 21-day cycle for a total of 4 cycles, patients will receive docetaxel (Taxotere) 75 mg/m\^2 IV plus cyclophosphamide (Cytoxan) 600 mg/m\^2 IV, plus weekly trastuzumab (Herceptin) 4 mg/kg IV (loading dose, Day 1, Cycle 1 only) and 2 mg/kg IV (on Days 1, 8, and 15) thereafter. Subsequent cycles of therapy will continue until a total of 4 cycles of TC+H have been completed. Then, patients will continue to receive trastuzumab 6 mg/kg every 3 weeks to complete 1 year of anti-HER2 therapy as per the current standard of care.
|
|---|---|
|
Overall Study
Adverse Event
|
44
|
|
Overall Study
Patient Request
|
21
|
|
Overall Study
Investigator Request
|
2
|
|
Overall Study
Disease Progression
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Other
|
13
|
Baseline Characteristics
Adj TC + Herceptin Early Stage Breast Cancer
Baseline characteristics by cohort
| Measure |
TC+H
n=493 Participants
docetaxel (Taxotere), plus cyclophosphamide (Cytoxan), plus weekly trastuzumab (Herceptin)
|
|---|---|
|
Age, Continuous
|
55.1 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
493 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
414 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
36 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
27 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
12 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Indian
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
493 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: ITT population. Patients were excluded if their TOP2A amplification were unknown.
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up.
Outcome measures
| Measure |
TOP2A-amplified Group
n=190 Participants
FISH ratio of TOP2A gene copy number was 2 or greater.
|
TOP2A-nonamplified Group
n=248 Participants
FISH ratio of TOP2A gene copy number was less than 2.
|
|---|---|---|
|
Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
|
0.978 probability of disease-free survival
Interval 0.942 to 0.992
|
0.979 probability of disease-free survival
Interval 0.949 to 0.991
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: ITT population. Patients were excluded if their TOP2A amplification were unknown.
OS is measured from the date of registration to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Outcome measures
| Measure |
TOP2A-amplified Group
n=190 Participants
FISH ratio of TOP2A gene copy number was 2 or greater.
|
TOP2A-nonamplified Group
n=248 Participants
FISH ratio of TOP2A gene copy number was less than 2.
|
|---|---|---|
|
Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
|
0.995 probability of overall survival
Interval 0.962 to 0.999
|
0.988 probability of overall survival
Interval 0.962 to 0.996
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: ITT population. Patients were excluded if their cMYC amplification were unknown.
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up.
Outcome measures
| Measure |
TOP2A-amplified Group
n=99 Participants
FISH ratio of TOP2A gene copy number was 2 or greater.
|
TOP2A-nonamplified Group
n=337 Participants
FISH ratio of TOP2A gene copy number was less than 2.
|
|---|---|---|
|
DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
|
0.968 probability of disease-free survival
Interval 0.904 to 0.99
|
0.981 probability of disease-free survival
Interval 0.958 to 0.991
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: ITT population. Patients were excluded if their cMYC amplification were unknown.
OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Outcome measures
| Measure |
TOP2A-amplified Group
n=99 Participants
FISH ratio of TOP2A gene copy number was 2 or greater.
|
TOP2A-nonamplified Group
n=337 Participants
FISH ratio of TOP2A gene copy number was less than 2.
|
|---|---|---|
|
OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
|
0.990 probability of overall survival
Interval 0.93 to 0.999
|
0.991 probability of overall survival
Interval 0.972 to 0.997
|
Adverse Events
TC+H
Serious events: 51 serious events
Other events: 481 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TC+H
n=486 participants at risk
docetaxel (Taxotere), plus cyclophosphamide (Cytoxan), plus weekly trastuzumab (Herceptin)
|
|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.41%
2/486 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Blood and lymphatic system disorders
ANEMIA
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Respiratory, thoracic and mediastinal disorders
ASPIRATION
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
BLOATING
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
BOWEL PERFORATION
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
CELLULITIS
|
0.82%
4/486 • Number of events 4 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
CELLULITIS BREAST
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
COLITIS
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
DEHYDRATION
|
1.0%
5/486 • Number of events 6 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
DIARRHEA
|
1.0%
5/486 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
DIVERTICULITIS
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
FEBRILE NEUTROPENIA
|
4.5%
22/486 • Number of events 23 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
FEVER
|
1.0%
5/486 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Cardiac disorders
FIBRILLATION ATRIAL
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
GASTRIC INFLAMMATION
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Hepatobiliary disorders
HEPATIC ENZYMES INCREASED
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Nervous system disorders
HYPERSENSITIVITY REACTION (NOS)
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Metabolism and nutrition disorders
HYPOKALEMIA
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
INFECTION
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Hepatobiliary disorders
LIVER FUNCTION TESTS MULTIPLE ABNORM
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Respiratory, thoracic and mediastinal disorders
LUNG FIBROSIS INTERSTITIAL
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
MASTITIS
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
MUCOSITIS NOS
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
NAUSEA
|
0.62%
3/486 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
NAUSEA AND VOMITING
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
0.82%
4/486 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
PAIN
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA
|
0.62%
3/486 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY INFILTRATION
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Nervous system disorders
SHOCK
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Respiratory, thoracic and mediastinal disorders
SHORTNESS OF BREATH
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Nervous system disorders
SYNCOPE
|
0.41%
2/486 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Vascular disorders
THROMBOSIS ARTERIAL LEG
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
VOMITING
|
0.21%
1/486 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
Other adverse events
| Measure |
TC+H
n=486 participants at risk
docetaxel (Taxotere), plus cyclophosphamide (Cytoxan), plus weekly trastuzumab (Herceptin)
|
|---|---|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
69.8%
339/486 • Number of events 395 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Blood and lymphatic system disorders
ANEMIA
|
27.0%
131/486 • Number of events 227 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
ANOREXIA
|
11.5%
56/486 • Number of events 69 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
13.6%
66/486 • Number of events 77 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Cardiac disorders
CARDIAC INSUFFICIENCY
|
6.0%
29/486 • Number of events 34 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
CONSTIPATION
|
18.5%
90/486 • Number of events 112 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
DIARRHEA
|
37.7%
183/486 • Number of events 276 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
DYSGUESIA
|
15.0%
73/486 • Number of events 86 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Blood and lymphatic system disorders
EDEMA
|
17.7%
86/486 • Number of events 120 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
FATIGUE
|
58.4%
284/486 • Number of events 487 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
FEVER
|
8.6%
42/486 • Number of events 55 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
GASTROESOPHAGEAL REFLUX
|
13.0%
63/486 • Number of events 68 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
HEADACHE
|
11.3%
55/486 • Number of events 67 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
HOT FLASHES
|
10.3%
50/486 • Number of events 59 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
INSOMNIA
|
10.1%
49/486 • Number of events 61 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Blood and lymphatic system disorders
LEUCOPENIA
|
17.3%
84/486 • Number of events 179 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Skin and subcutaneous tissue disorders
MUCOSAL
|
6.6%
32/486 • Number of events 39 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Infections and infestations
MUCOSITIS
|
18.3%
89/486 • Number of events 115 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
16.7%
81/486 • Number of events 96 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Skin and subcutaneous tissue disorders
NAIL DISORDER
|
7.0%
34/486 • Number of events 38 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
NAUSEA
|
44.4%
216/486 • Number of events 315 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Nervous system disorders
NEUROPATHY
|
20.4%
99/486 • Number of events 125 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
50.8%
247/486 • Number of events 597 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
General disorders
PAIN
|
13.2%
64/486 • Number of events 91 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Skin and subcutaneous tissue disorders
RASH
|
21.4%
104/486 • Number of events 141 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Respiratory, thoracic and mediastinal disorders
SHORTNESS OF BREATH
|
8.4%
41/486 • Number of events 46 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
|
Gastrointestinal disorders
VOMITING
|
9.3%
45/486 • Number of events 53 • During the whole treatment period, up to 30 days following last dose.
For treated patients only, assessed at each treatment visit.
|
Additional Information
Dr. Stephen E Jones
US Oncology Research, McKesson Specialty Health
Phone: 832-381-7580
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place