Trial Outcomes & Findings for A Study of Herceptin (Trastuzumab) in Combination With 2nd-Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer. (NCT NCT00444587)
NCT ID: NCT00444587
Last Updated: 2016-06-21
Results Overview
Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
114 participants
Primary outcome timeframe
Up to 5 years
Results posted on
2016-06-21
Participant Flow
A total of 114 participants were enrolled in this study conducted from March 2007 to August 2011 at 30 centers in 8 countries.
Of 114 participants screened, 3 participants were screening failures. The reasons for screening failure were violation of inclusion criteria, refused to take part in the study and bacterial infection. Therefore, 111 participants were randomized to receive study treatment. Two participants were randomized but never started study treatment.
Participant milestones
| Measure |
Trastuzumab + 2nd Line Chemotherapy
Eligible participants were administered trastuzumab (Herceptin) 6 milligrams per kilograms (mg/kg) of body weight (except in Israel, where the dose was 2 mg/kg body weight), intravenous (IV) infusion every three weeks until disease progression, unacceptable toxicities, or withdrawal from study, in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Overall Study
STARTED
|
93
|
16
|
|
Overall Study
COMPLETED
|
10
|
1
|
|
Overall Study
NOT COMPLETED
|
83
|
15
|
Reasons for withdrawal
| Measure |
Trastuzumab + 2nd Line Chemotherapy
Eligible participants were administered trastuzumab (Herceptin) 6 milligrams per kilograms (mg/kg) of body weight (except in Israel, where the dose was 2 mg/kg body weight), intravenous (IV) infusion every three weeks until disease progression, unacceptable toxicities, or withdrawal from study, in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Overall Study
Death
|
2
|
1
|
|
Overall Study
Progression of the disease
|
73
|
8
|
|
Overall Study
Refused treatment/did not cooperate
|
4
|
1
|
|
Overall Study
Investigator decision
|
3
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Missing
|
0
|
5
|
Baseline Characteristics
A Study of Herceptin (Trastuzumab) in Combination With 2nd-Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer.
Baseline characteristics by cohort
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
n=16 Participants
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
Total
n=109 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.4 years
STANDARD_DEVIATION 12.8 • n=5 Participants
|
56.3 years
STANDARD_DEVIATION 10.2 • n=7 Participants
|
55.5 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
93 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 5 yearsPopulation: The Full-Analysis-Set included all participants who were enrolled and had at least one valid primary efficacy variable on active treatment. n = Numbers of participants included in this analysis.
Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=73 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Median Time to Disease Progression
By Computer (n = 65)
|
171 Days
Interval 136.0 to 322.0
|
—
|
|
Median Time to Disease Progression
By Investigator (n = 73)
|
171 Days
Interval 136.0 to 265.0
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The Full-Analysis-Set participants with measurable disease with CR or PR
Objective response rate (ORR) is defined as the percentage of participants with tumor shrinkage of a predefined amount. It is a combination of complete response (CR) and partial response (PR) and was assessed according to the RECIST criteria 1.0. Complete response refers to the disappearance of all target lesions and all non-target non-measurable lesions. Partial Response refers to an at least 30 percent decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. Objective response rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=87 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Objective Response Rate
By Investigator (n= 87)
|
43.7 Percentage of participants
Interval 33.1 to 54.8
|
—
|
|
Objective Response Rate
By computer (n=87)
|
43.7 Percentage of participants
Interval 33.1 to 54.8
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The Full-Analysis-Set participants with measurable disease with CR, PR and SD. Study design was changed to single arm study because herceptin use after progression herceptin-based therapy become widespread.
Clinical benefit rate (CBR) was defined as the percentage of participants taking a benefit from the treatments. CBR includes 1) Complete response (CR): disappearance of all target lesions and all non-target non-measurable lesions 2) Partial response (PR) : \>=30% decrease in the sum of the longest diameter of target lesions and 3) Stable disease (SD): non-PR and non-progressive disease. It was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by CT or MRI by the investigator. CBR was also assessed by computer. Clinical benefit rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=87 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Clinical Benefit Rate
By Computer (n = 87)
|
75.9 Percentage of participants
Interval 65.5 to 84.4
|
—
|
|
Clinical Benefit Rate
By Investigator (n = 87)
|
72.4 Percentage of participants
Interval 61.8 to 81.5
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The Full-Analysis-Set included all participants who were enrolled and had at least one valid primary efficacy variable on active treatment. Only those participants who experienced treatment failure were analyzed.
Time to treatment failure is defined as a composite endpoint measuring time (number of days) from enrollment to discontinuation of treatment or change in treatment for any reason, including disease progression, treatment toxicity and death. Median time to treatment failure was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=80 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Median Time to Treatment Failure
|
154 Days
Interval 131.0 to 238.0
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The Full-Analysis-Set included all participants who were enrolled and had at least one valid primary efficacy variable on active treatment. Only those participants with data available were analyzed.
Overall Survival is defined as the time (number of days) between enrollment and the date of death due to any cause. Overall survival was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=41 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Overall Survival
|
717 Days
Interval 589.0 to 1057.0
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
n=16 Participants
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Number of Participants With Any Adverse Events and Serious Adverse Events
Number of participants with any AE
|
84 Number of participants
|
10 Number of participants
|
|
Number of Participants With Any Adverse Events and Serious Adverse Events
Number of participants with any SAE
|
20 Number of participants
|
2 Number of participants
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkali phosphatase (ALP) at Visit 1 and final study assessments (Up to 5 years). Serum glutamic oxaloacetic transaminase, Serum glutamic-pyruvic transaminase and Alkali Phosphatase levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
SGOT, Visit 1, (n = 93)
|
31.46 Units per liter
Standard Deviation 29.78
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
SGOT, Final study assessments, (n = 62)
|
36.16 Units per liter
Standard Deviation 34.91
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
SGPT, Visit 1, (n = 93)
|
25.86 Units per liter
Standard Deviation 20.55
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
SGPT, Final study assessments, (n = 61)
|
28.19 Units per liter
Standard Deviation 16.92
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
ALP, Visit 1, (n = 93)
|
202.30 Units per liter
Standard Deviation 149.98
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels
ALP, Final study assessments, (n = 62)
|
193.49 Units per liter
Standard Deviation 148.11
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the total bilirubin and serum creatinine. Total Bilirubin and serum creatinine levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Total bilirubin, Visit 1, (n = 93)
|
13.50 Micromole/liter
Standard Deviation 42.74
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Total bilirubin, Final study assessments(n = 60)
|
19.16 Micromole/liter
Standard Deviation 36.77
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Serum creatinine, Visit 1, (n = 92)
|
81.18 Micromole/liter
Standard Deviation 61.75
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels
Serum creatinine,Final study assessment (n = 63)
|
82.53 Micromole/liter
Standard Deviation 70.86
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the albumin at Visit 1 and Final study assessments. Albumin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=84 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Biochemistry Safety Laboratory Parameters: Mean Albumin Levels
Albumin, Visit 1, (n = 84)
|
43.99 gram per liter
Standard Deviation 3.29
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Albumin Levels
Albumin, Final study assessments, (n = 54)
|
41.07 gram per liter
Standard Deviation 6.96
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the biochemical safety laboratory parameters urea, sodium and potassium. Urea, sodium and potassium levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=92 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Urea, Visit 1, (n = 92)
|
6.33 Millimole per liter
Standard Deviation 3.07
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Urea, Final study assessments, (n = 63)
|
6.92 Millimole per liter
Standard Deviation 4.93
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Sodium, Visit 1, (n = 92)
|
140.58 Millimole per liter
Standard Deviation 3.34
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Sodium, Final study assessments, (n = 61)
|
139.16 Millimole per liter
Standard Deviation 3.71
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Potassium, Visit 1, (n = 91)
|
4.40 Millimole per liter
Standard Deviation 0.45
|
—
|
|
Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels
Potassium, Final study assessments, (n = 61)
|
4.22 Millimole per liter
Standard Deviation 0.40
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the Hemoglobin up to 5 years. Hemoglobin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels
Hemoglobin, Visit 1, (n = 93)
|
12.67 grams per deciliter
Standard Deviation 2.03
|
—
|
|
Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels
Hemoglobin, Final study assessments, (n = 67)
|
11.00 grams per deciliter
Standard Deviation 3.57
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the total leukocytes up to 5 years. Total leukocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=92 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts
Total Leukocytes, Visit 1, (n = 92)
|
8.00 10^9 leukocytes/L
Standard Deviation 8.60
|
—
|
|
Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts
Total Leukocytes, Final study assessment (n =67)
|
7.53 10^9 leukocytes/L
Standard Deviation 6.88
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes at Visit 1 and final study assessments. Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Neutrophils, Visit 1, (n = 93)
|
64.89 percent of differential
Standard Deviation 10.66
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Neutrophils, Final study assessments, (n = 64)
|
62.22 percent of differential
Standard Deviation 14.80
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Basophils, Visit 1, (n = 86)
|
0.38 percent of differential
Standard Deviation 0.33
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Basophils, Final study assessments, (n = 59)
|
1.28 percent of differential
Standard Deviation 6.34
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Eosinophils, Visit 1, (n = 88)
|
2.36 percent of differential
Standard Deviation 2.15
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Eosinophils, Final study assessments, (n = 61)
|
2.50 percent of differential
Standard Deviation 3.56
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Lymphocytes, Visit 1, (n = 93)
|
26.34 percent of differential
Standard Deviation 9.37
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Lymphocytes, Final study assessments, (n = 64)
|
26.48 percent of differential
Standard Deviation 12.85
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Monocytes, Visit 1, (n = 89)
|
5.92 percent of differential
Standard Deviation 2.22
|
—
|
|
Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts
Monocytes, Final study assessments, (n = 59)
|
7.25 percent of differential
Standard Deviation 3.56
|
—
|
SECONDARY outcome
Timeframe: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years)Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Participants in the study were evaluated for the platelets at Visit 1 and final study assessments. Platelet counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Hematology Safety Laboratory Parameter: Mean Platelets Counts
Platelets, Visit 1, (n = 93)
|
263.14 Number of cells x 10^9/L
Standard Deviation 63.91
|
—
|
|
Hematology Safety Laboratory Parameter: Mean Platelets Counts
Platelets, Final study assessments, (n = 67)
|
256.64 Number of cells x 10^9/L
Standard Deviation 78.64
|
—
|
SECONDARY outcome
Timeframe: Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).Population: The Safety Population included all participants who entered the trial and received at least one dose of trial medication. n = the number of participants analyzed at a given time point.
Left ventricular ejection fraction (LVEF) is a measure of the percent of blood ejected from the ventricle in one heartbeat. It is a measure of cardiac function and was assessed by echocardiogram or multigated angiogram at Visit 0 \[Screening period (6 weeks prior to enrollment)\] and final study assessments (Up to 5 years).
Outcome measures
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=92 Participants
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
n=16 Participants
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Mean Left Ventricular Ejection Fraction
Visit 0 (n = 92, 16)
|
63.3 percent of blood pumped from LV chamber]
Standard Deviation 6.8
|
62.6 percent of blood pumped from LV chamber]
Standard Deviation 6.9
|
|
Mean Left Ventricular Ejection Fraction
Final study assessment (n= 53, 5)
|
61.2 percent of blood pumped from LV chamber]
Standard Deviation 7.4
|
68.6 percent of blood pumped from LV chamber]
Standard Deviation 5.9
|
Adverse Events
Trastuzumab + 2nd Line Chemotherapy
Serious events: 20 serious events
Other events: 81 other events
Deaths: 0 deaths
Only Chemotherapy
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 participants at risk
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
n=16 participants at risk
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Blood and lymphatic system disorders
Granulocytosis
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Atrial fibrillation
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Cardiopulmonary failure
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Eye disorders
Retinal detachment
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Nausea
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Vomiting
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Chest pain
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Death
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Pyrexia
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Gastroenteritis
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Pneumonia
|
5.4%
5/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Sepsis
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Urinary tract infection
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Brain oedema
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Vascular disorders
Superior vena cava syndrome
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
Other adverse events
| Measure |
Trastuzumab + 2nd Line Chemotherapy
n=93 participants at risk
Eligible participants were administered trastuzumab 6 mg/kg of body weight (except in Israel, where the dose was 2 mg/kg body weight), IV infusion, every three weeks until disease progression, unacceptable toxicities, or withdrawal from study in combination with second line chemotherapy.
|
Only Chemotherapy
n=16 participants at risk
Eligible participants were administered second line chemotherapy according to the investigator's decision.
|
|---|---|---|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Polyneuropathy
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Psychiatric disorders
Confusional state
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Psychiatric disorders
Depression
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Psychiatric disorders
Insomnia
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Renal and urinary disorders
Dysuria
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Reproductive system and breast disorders
Breast pain
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.2%
16/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.8%
11/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.5%
6/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.8%
10/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
12.9%
12/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
12.5%
2/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
39.8%
37/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
25.0%
4/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.8%
11/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Scar pain
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Vascular disorders
Deep vein thrombosis
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Vascular disorders
Hypertension
|
20.4%
19/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Vascular disorders
Phlebitis
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Agranulocytosis
|
5.4%
5/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Anemia
|
26.9%
25/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
31.2%
5/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Granulocytopenia
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
12.5%
2/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Leukopenia
|
81.7%
76/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
18.8%
3/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Neutropenia
|
86.0%
80/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Cardiac failure
|
6.5%
6/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Cardiomyopathy
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Palpitations
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Cardiac disorders
Tachycardia
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Eye disorders
Cataract
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Eye disorders
Keratitis
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Eye disorders
Lacrimation increased
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
12.9%
12/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Constipation
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
55.9%
52/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Dyspepsia
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Flatulence
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Nausea
|
57.0%
53/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Stomatitis
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Toothache
|
1.1%
1/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Gastrointestinal disorders
Vomiting
|
22.6%
21/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Asthenia
|
16.1%
15/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Chest pain
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Chills
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Face oedema
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Fatigue
|
32.3%
30/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
43.8%
7/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Gait disturbance
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Infusion site inflammation
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Infusion site pain
|
7.5%
7/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Local swelling
|
0.00%
0/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Oedema peripheral
|
8.6%
8/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
25.0%
4/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Pain
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Peripheral swelling
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
General disorders
Pyrexia
|
11.8%
11/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Immune system disorders
Hypersensitivity
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Bronchitis
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Cellulitis
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Conjunctivitis
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Cystitis
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Erysipelas
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Eye infection
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Herpes zoster
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Infection
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Pharyngitis
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Pneumonia
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.5%
6/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Urinary tract infection
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Infections and infestations
Viral infection
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Investigations
Blood bilirubin increased
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Investigations
Blood glucose increased
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Investigations
Ejection fraction decreased
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Investigations
Hepatic enzyme increased
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Investigations
Weight decreased
|
5.4%
5/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.1%
15/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.5%
6/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.5%
7/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
14.0%
13/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.2%
3/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.5%
6/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
12.5%
2/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Dizziness
|
14.0%
13/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
6.2%
1/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Dysgeusia
|
2.2%
2/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Headache
|
8.6%
8/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Hypoaesthesia
|
10.8%
10/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Neuropathy peripheral
|
5.4%
5/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
18.8%
3/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
|
Nervous system disorders
Paraesthesia
|
4.3%
4/93 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
0.00%
0/16 • Up to 5 years
The Safety Population included all participants who entered the trial and received at least one dose of trial medication.
|
Additional Information
Roche Trial Information Hotline
F. Hoffmann-La Roche AG
Phone: +41 616878333
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER