Trial Outcomes & Findings for Effects of Granulocyte Colony-stimulating Factor (G-CSF), Trastuzumab, and Vinorelbine on Immune Cell Function (NCT NCT00169104)
NCT ID: NCT00169104
Last Updated: 2018-07-20
Results Overview
Buffy coat effector cells were isolated by centrifugation from heparinized blood, and washed and counted. SKBR3 target cells were labeled with 51-Cr at 100 uCi per 5 x 105 cells for 1 hour at 37 C, washed and effector cells and target cells were plated at a ratio of 70:1 in 96 well microtiter plates, with trastuzumab 2 ug/ml and with no antibody. After addition of the target cells, the plate was centrifuged gently at 1200 rpm to pellet cells, the plate was incubated for 4 hours at 37C, and 100 uL of supernatant was measured on a gamma counter set for 51Cr counting for 1 minute per tube. Specific lysis in % is defined as follows: % specific lysis = (counts released into the supernatant under experimental conditions - spontaneous counts released into the supernatant) / (maximum counts released into the supernatant - spontaneous counts released into the supernatant) Specific lysis at Day 12 was compared to specific lysis at baseline between the G-CSF group and the placebo group.
Recruitment status
TERMINATED
Study phase
PHASE2/PHASE3
Target enrollment
23 participants
Primary outcome timeframe
Baseline and 12 days
Results posted on
2018-07-20
Participant Flow
Patients were enrolled between July 12, 2002 and November 2, 2007 from the Comprehensive Breast Program at the Norris Cotton Cancer Center.
There was no run-in prior to randomization and the start of treatment.
Participant milestones
| Measure |
G-CSF Arm
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
|
Placebo Arm
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
10
|
|
Overall Study
COMPLETED
|
11
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
G-CSF Arm
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
|
Placebo Arm
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Effects of Granulocyte Colony-stimulating Factor (G-CSF), Trastuzumab, and Vinorelbine on Immune Cell Function
Baseline characteristics by cohort
| Measure |
G-CSF Arm
n=11 Participants
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
|
Placebo Arm
n=8 Participants
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
|
Total
n=19 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
|
10 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
51.0 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
53.9 years
STANDARD_DEVIATION 12.6 • n=7 Participants
|
52.2 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 daysPopulation: 19 subjects were evaluable for response and toxicity, but only 17 subjects had evaluable specific lysis laboratory outcomes at baseline and at Day 12.
Buffy coat effector cells were isolated by centrifugation from heparinized blood, and washed and counted. SKBR3 target cells were labeled with 51-Cr at 100 uCi per 5 x 105 cells for 1 hour at 37 C, washed and effector cells and target cells were plated at a ratio of 70:1 in 96 well microtiter plates, with trastuzumab 2 ug/ml and with no antibody. After addition of the target cells, the plate was centrifuged gently at 1200 rpm to pellet cells, the plate was incubated for 4 hours at 37C, and 100 uL of supernatant was measured on a gamma counter set for 51Cr counting for 1 minute per tube. Specific lysis in % is defined as follows: % specific lysis = (counts released into the supernatant under experimental conditions - spontaneous counts released into the supernatant) / (maximum counts released into the supernatant - spontaneous counts released into the supernatant) Specific lysis at Day 12 was compared to specific lysis at baseline between the G-CSF group and the placebo group.
Outcome measures
| Measure |
G-CSF Arm
n=10 Participants
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
G-CSF: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
Placebo Arm
n=7 Participants
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
saline placebo: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
|---|---|---|
|
Antibody Dependent Cell-mediated Cytotoxicity of Effector Cells Isolated From Subjects Receiving Trastuzumab With Either G-CSF or a Saline Placebo Against a Her-2 Overexpressing Target in Vitro
|
1.47 percentage of specific lysis
Standard Deviation 0.97
|
1.67 percentage of specific lysis
Standard Deviation 2.34
|
SECONDARY outcome
Timeframe: Baseline and 14 weeksPopulation: 17 of 19 subjects had results from ADCC assays from baseline and at week 14. Because subjects on both arms of the trial received the identical treatment with 12 weeks of vinorelbine and G-CSF after the initial two week randomization, it is appropriate to pool the results of the ADCC assays at the 14 week timepoint from both arms.
Buffy coat effector cells were isolated by centrifugation from heparinized blood, washed, and counted. SKBR3 target cells were labeled with 51-Cr at 100 uCi per 5 x 105 cells for 1 hour at 37 C, washed and effector cells and target cells were plated at a ratio of 70:1 in 96 well microtiter plates, with trastuzumab 2 ug/ml and with no antibody. After addition of the target cells, the plate was centrifuged gently at 1200 rpm to pellet cells, the plate was incubated for 4 hours at 37C, and 100 uL of supernatant was measured on a gamma counter set for 51Cr counting for 1 minute per tube. Specific lysis in % is defined as follows: % specific lysis = (counts released into the supernatant under experimental conditions - spontaneous counts released into the supernatant) / (maximum counts released into the supernatant - spontaneous counts released into the supernatant) Specific lysis at Week 14 was compared to specific lysis at baseline for 17 patients with week 14 samples available.
Outcome measures
| Measure |
G-CSF Arm
n=17 Participants
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
G-CSF: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
Placebo Arm
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
saline placebo: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
|---|---|---|
|
Antibody Dependent Cell-mediated Cytotoxicity of Effector Cells Isolated From Subjects Receiving Chemotherapy, Trastuzumab, and G-CSF Against a Her-2 Overexpressing Target in Vitro
|
1.67 percentage of specific lysis
Standard Deviation 3.47
|
—
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: 19 subjects completed 14 weeks of treatment and underwent restaging at that timepoint.
19 subjects (11 on the G-CSF arm and 8 on the placebo arm) completed 14 weeks of treatment and completed restaging at that time. Responses were evaluated by RECIST criteria.
Outcome measures
| Measure |
G-CSF Arm
n=11 Participants
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
G-CSF: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
Placebo Arm
n=8 Participants
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
saline placebo: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
|---|---|---|
|
Clinical Response Rate of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Complete Response
|
0 Participants
|
0 Participants
|
|
Clinical Response Rate of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Partial Response
|
1 Participants
|
4 Participants
|
|
Clinical Response Rate of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Stable Disease
|
2 Participants
|
3 Participants
|
|
Clinical Response Rate of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Disease Progression
|
8 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: 19 subjects (11 on the G-CSF arm and 8 on the placebo arm) received at least two weeks of treatment on study and were evaluable for toxicity.
Adverse events were graded per RECIST v4.0. There were two severe adverse events: Grade 3 mental status changes in one subject on the G-CSF arm, and Grade 3 febrile neutropenia in one subject on the Placebo arm. Refer to Adverse Events Table for specifics.
Outcome measures
| Measure |
G-CSF Arm
n=11 Participants
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
G-CSF: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
Placebo Arm
n=8 Participants
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
saline placebo: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
|---|---|---|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 elevation in AST
|
0 Participants
|
2 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 mental status changes
|
1 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 febrile neutropenia
|
0 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 4 leukopenia
|
2 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 4 granulocytopenia
|
1 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 anemia
|
3 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 thrombocytopenia
|
1 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 granulocytopenia
|
2 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 elevation in alkaline phosphatase
|
2 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 elevation in AST
|
1 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 3 elevation in ALT
|
0 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 sensory neuropathy
|
1 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 arthralgias
|
0 Participants
|
2 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 constipation
|
1 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 tumor pain
|
0 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 mucositis
|
0 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 heartburn
|
1 Participants
|
0 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 anemia
|
5 Participants
|
4 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 thrombocytopenia
|
0 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 leukopenia
|
3 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 granulocytopenia
|
1 Participants
|
1 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 elevation in alkaline phosphatase
|
5 Participants
|
2 Participants
|
|
Safety of the Combination of Trastuzumab, G-CSF, and Vinorelbine in Subjects With Her-2 Overexpressing Metastatic Breast Cancer
Grade 2 elevation in ALT
|
0 Participants
|
1 Participants
|
Adverse Events
G-CSF
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
{Placebo
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
G-CSF
n=11 participants at risk
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
G-CSF: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
{Placebo
n=8 participants at risk
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
saline placebo: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
|---|---|---|
|
Nervous system disorders
Mental status change
|
9.1%
1/11 • Number of events 1 • 14 weeks
|
0.00%
0/8 • 14 weeks
|
|
Immune system disorders
Febrile neutropenia
|
0.00%
0/11 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
Other adverse events
| Measure |
G-CSF
n=11 participants at risk
Subjects will receive ten doses of G-CSF at a dose of 5 mcgm/kg daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg IV weeks 3 through 14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13 and G-CSF at 5 mcgm/kg SQ daily Monday through Friday weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
G-CSF: 5 mcgm/kg SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
{Placebo
n=8 participants at risk
Subjects will receive ten doses of a placebo injection SQ daily Monday through Friday for the first two weeks of the trial. All patients will also receive trastuzumab at 4 mg/kg week 1, and 2 mg/kg week 2 during the first two weeks of the trial. All patients will then receive 12 weeks of trastuzumab at 2 mg/kg weeks 3-14, vinorelbine at 25 mg/m2 IV weekly weeks 3,4,6,7,9,10,12,13, and G-CSF at 5 mcgm/kg SQ daily Monday through Fridays weeks 3-14.
G-CSF: 5 mcgm/kg daily Monday through Friday weeks 3-14
trastuzumab: 4 mcgm/kg intravenously (IV) over 90 minutes week 1, then 2 mg/kg IV over 30 minutes weeks 2-14
vinorelbine: 25 mg/m2 over 6 minutes IV weekly, weeks 3, 4, 6, 7, 9, 10, 12, 13
saline placebo: Saline will be given SQ daily for ten days, Monday through Friday of the first two weeks of the study
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/11 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Blood and lymphatic system disorders
Anemia
|
27.3%
3/11 • Number of events 3 • 14 weeks
|
0.00%
0/8 • 14 weeks
|
|
Nervous system disorders
Sensory neuropathy
|
9.1%
1/11 • Number of events 1 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgias
|
0.00%
0/11 • 14 weeks
|
25.0%
2/8 • Number of events 2 • 14 weeks
|
|
Gastrointestinal disorders
constipation
|
9.1%
1/11 • Number of events 1 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Blood and lymphatic system disorders
anemia
|
45.5%
5/11 • Number of events 5 • 14 weeks
|
50.0%
4/8 • Number of events 4 • 14 weeks
|
|
Nervous system disorders
Tumor pain
|
0.00%
0/11 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/11 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Gastrointestinal disorders
heartburn
|
9.1%
1/11 • Number of events 1 • 14 weeks
|
0.00%
0/8 • 14 weeks
|
|
Blood and lymphatic system disorders
Leukopenia
|
27.3%
3/11 • Number of events 3 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Blood and lymphatic system disorders
Granulocytopenia
|
9.1%
1/11 • Number of events 1 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
|
Investigations
Elevated alkaline phosphatase
|
45.5%
5/11 • Number of events 5 • 14 weeks
|
25.0%
2/8 • Number of events 2 • 14 weeks
|
|
Investigations
Elevated AST
|
0.00%
0/11 • 14 weeks
|
25.0%
2/8 • Number of events 2 • 14 weeks
|
|
Investigations
Elevated ALT
|
0.00%
0/11 • 14 weeks
|
12.5%
1/8 • Number of events 1 • 14 weeks
|
Additional Information
Gary N. Schwartz MD
Dartmouth-Hitchcock Medical Center / Norris Cotton Cancer Center
Phone: (603) 653-6181
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor will be provided 30 days to review a manuscript and 15 days to review a poster. The sponsor may request an additional 60 days to review study results prior to their release, if the request is submitted in writing.
- Publication restrictions are in place
Restriction type: OTHER