Trial Outcomes & Findings for Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression (NCT NCT00033514)
NCT ID: NCT00033514
Last Updated: 2020-10-08
Results Overview
Complete Response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission. Partial Response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
27 participants
Primary outcome timeframe
5 years
Results posted on
2020-10-08
Participant Flow
Participant milestones
| Measure |
Treatment Phase 1
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
|
Treatment Phase 2
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
11
|
|
Overall Study
COMPLETED
|
15
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
4
|
Reasons for withdrawal
| Measure |
Treatment Phase 1
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
|
Treatment Phase 2
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
3
|
Baseline Characteristics
Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression
Baseline characteristics by cohort
| Measure |
Treatment Phase 1
n=16 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
|
Treatment Phase 2
n=11 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
11 participants
n=7 Participants
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 5 yearsPopulation: 12 patients with measurable disease and no prior trastuzumab in the metastatic setting considered evaluable at the recommended phase II dose level. 2 from phase 1 and 10 from phase 2 Excluded : 14 from Phase I: no measureable disease or previous trastuzumab. Phase II: Withdrawn due to disease complications
Complete Response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission. Partial Response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
Outcome measures
| Measure |
Treatment Phase 1 Plus Phase 2
n=12 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 150 mg daily.
|
|---|---|
|
The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.
Partial Response
|
4 participants
|
|
The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.
Stable Disease
|
1 participants
|
PRIMARY outcome
Timeframe: treatment periodPopulation: patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.
Outcome measures
| Measure |
Treatment Phase 1 Plus Phase 2
n=14 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 150 mg daily.
|
|---|---|
|
Recommended Dose for Phase II
50 dose mg/day
|
6 participants receiving each dose
|
|
Recommended Dose for Phase II
100 dose mg/day
|
3 participants receiving each dose
|
|
Recommended Dose for Phase II
150 dose mg/day
|
5 participants receiving each dose
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Subjects that achieved objective response (4). All were from phase II.
Outcome measures
| Measure |
Treatment Phase 1 Plus Phase 2
n=4 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 150 mg daily.
|
|---|---|
|
Duration of Objective Response
greater than 6 months
|
4 participants
|
|
Duration of Objective Response
greater than 2 years
|
2 participants
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: subjects evaluated for Serious Adverse Events (SAEs)
Outcome measures
| Measure |
Treatment Phase 1 Plus Phase 2
n=27 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 150 mg daily.
|
|---|---|
|
Incidence of Adverse Events
|
16 participants affected by SAEs
|
SECONDARY outcome
Timeframe: 4 monthsOutcome measures
| Measure |
Treatment Phase 1 Plus Phase 2
n=10 Participants
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 150 mg daily.
|
|---|---|
|
Serum Concentration of Herceptin at Specified Time-points.
Day 7 peak
|
98.4 mcg/mL
Interval 64.8 to 132.0
|
|
Serum Concentration of Herceptin at Specified Time-points.
Day 7 trough
|
46 mcg/mL
Interval 32.2 to 59.8
|
|
Serum Concentration of Herceptin at Specified Time-points.
Day 14 peak
|
86 mcg/mL
Interval 67.4 to 105.0
|
|
Serum Concentration of Herceptin at Specified Time-points.
Day 14 trough
|
46.9 mcg/mL
Interval 31.4 to 62.4
|
|
Serum Concentration of Herceptin at Specified Time-points.
Day 21 peak
|
88.3 mcg/mL
Interval 66.9 to 110.0
|
|
Serum Concentration of Herceptin at Specified Time-points.
Day 21 trough
|
50.8 mcg/mL
Interval 35.6 to 66.0
|
Adverse Events
Treatment Phase 1 Plus Phase 2
Serious events: 16 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment Phase 1 Plus Phase 2
n=27 participants at risk
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 50mg daily, 100 mg daily and 150 mg daily.
|
|---|---|
|
Gastrointestinal disorders
dehydration/pain management
|
3.7%
1/27 • Number of events 1 • 9.4 years
|
|
Cardiac disorders
Dyspnea
|
22.2%
6/27 • Number of events 6 • 9.4 years
|
|
Cardiac disorders
hypertension with headache
|
3.7%
1/27 • Number of events 1 • 9.4 years
|
|
Cardiac disorders
pain/chest pressure/SOB
|
3.7%
1/27 • Number of events 1 • 9.4 years
|
|
Cardiac disorders
LVEF less than the lower limit of normal
|
7.4%
2/27 • Number of events 2 • 9.4 years
|
|
General disorders
progressive brain mets
|
7.4%
2/27 • Number of events 2 • 9.4 years
|
|
Gastrointestinal disorders
gastroenteritis
|
3.7%
1/27 • Number of events 1 • 9.4 years
|
|
Skin and subcutaneous tissue disorders
maculopapular rash
|
3.7%
1/27 • Number of events 1 • 9.4 years
|
|
Cardiac disorders
subendocardial myocardial infarction
|
3.7%
1/27 • Number of events 1 • 9.4 years
|
Other adverse events
| Measure |
Treatment Phase 1 Plus Phase 2
n=27 participants at risk
trastuzumab: Day 1 4mg/kg IV 2 mg/kg IV weekly.
erlotinib hydrochloride: 50mg daily, 100 mg daily and 150 mg daily.
|
|---|---|
|
Skin and subcutaneous tissue disorders
alopecia
|
14.8%
4/27 • Number of events 4 • 9.4 years
|
|
Blood and lymphatic system disorders
anemia
|
11.1%
3/27 • Number of events 3 • 9.4 years
|
|
Gastrointestinal disorders
anorexia
|
44.4%
12/27 • Number of events 12 • 9.4 years
|
|
Gastrointestinal disorders
diarrhea
|
81.5%
22/27 • Number of events 22 • 9.4 years
|
|
Skin and subcutaneous tissue disorders
dry skin
|
37.0%
10/27 • Number of events 10 • 9.4 years
|
|
Gastrointestinal disorders
dysgeusia
|
14.8%
4/27 • Number of events 4 • 9.4 years
|
|
Gastrointestinal disorders
dyspepsia
|
11.1%
3/27 • Number of events 3 • 9.4 years
|
|
Metabolism and nutrition disorders
elevated transaminases
|
11.1%
3/27 • Number of events 3 • 9.4 years
|
|
Blood and lymphatic system disorders
epistaxis
|
11.1%
3/27 • Number of events 3 • 9.4 years
|
|
General disorders
fatigue
|
40.7%
11/27 • Number of events 11 • 9.4 years
|
|
General disorders
fever
|
11.1%
3/27 • Number of events 3 • 9.4 years
|
|
General disorders
headache
|
14.8%
4/27 • Number of events 4 • 9.4 years
|
|
Gastrointestinal disorders
nausea
|
37.0%
10/27 • Number of events 10 • 9.4 years
|
|
Skin and subcutaneous tissue disorders
pruitus
|
48.1%
13/27 • Number of events 13 • 9.4 years
|
|
Gastrointestinal disorders
stomatitis
|
37.0%
10/27 • Number of events 10 • 9.4 years
|
|
Skin and subcutaneous tissue disorders
rash
|
81.5%
22/27 • Number of events 22 • 9.4 years
|
|
Gastrointestinal disorders
vomiting
|
11.1%
3/27 • Number of events 3 • 9.4 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place