Breast Cancer
Conditions
Brief summary
This single-arm study was designed to evaluate the efficacy and safety of oral Xeloda plus intravenous Avastin as first-line treatment in women with metastatic breast cancer. Patients received Xeloda 1000 mg/m² orally (PO) twice daily (BID) on Days 1-15, and Avastin 15 mg intravenously (IV) on Day 1 of each 3-week cycle. The anticipated time on study treatment was until disease progression or unacceptable toxicity. The target sample size was \<100 individuals.
Interventions
DRUGCapecitabine
1000 mg/m² PO BID on Days 1-15 of each 3-week cycle
DRUGBevacizumab
15 mg IV on Day 1 of each 3-week cycle
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women \>=18 years of age * HER2-negative metastatic breast cancer * Previous adjuvant chemotherapy or hormonal treatment * \>=1 measurable target lesion
Exclusion criteria
* Previous treatment with chemotherapy, an anti-angiogenic agent, or a biologic therapy for advanced or metastatic cancer * Radiation therapy within 4 weeks of study treatment start or insufficient recovery from the effects of prior radiation therapy * Central nervous system metastases * Other malignancy within last 5 years, except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix * Serious concurrent infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | approximately 505 days (Median Time to Death) | Overall survival was defined as the time from date of first treatment dose (Day 1) to date of death, across the study phases regardless of the cause of death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | Throughout study | The secondary outcome measure was to evaluate the safety profile, including a summary of adverse events (AEs) assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Intensity of AEs were graded according to NCI CTCAE version 3.0 on a 5-point scale: Grade 1=Mild Discomfort, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life Threatening/Disabling and Grade 5=Death. An SAE was defined as any experience that suggested a significant hazard,contraindication, side effect, or precaution. |
| Premature Withdrawal From Study Due to Adverse Events | Throughout study | The secondary outcome measure was to evaluate the safety profile, including a summary of premature withdrawals due to adverse events occurring in more than 1 patient in either study group, by system organ class. |
| Number of Participants With Marked Laboratory Abnormalities | until progressive disease or for up to 3 years | The secondary outcome measure was to evaluate the safety profile, including a summary of marked laboratory abnormalities in \>= 5% of patients. n=number of participants with the laboratory measure,Number=number of participants with the abnormality. Laboratory values were flagged as Low(L) or High(H) if they were below the lower limit or above the upper limit of Roche standard reference range, respectively. Marked laboratory abnormalities (flagged as HH and LL) were defined as those values that were outside the Roche marked reference range and showed a clinically relevant change from baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev First Study Treatment Phase:
Capecitabine 1000 mg/m² oral (PO) twice-daily, Days 1-15 of each 3-week cycle (28 doses per cycle); bevacizumab 15 mg/kg intravenous (IV) infusion, Day 1 of each 3-week cycle.
Second Study Treatment Phase:
Paclitaxel 80 mg/m² 60-minute IV infusion (with appropriate premedication), Days 1, 8 and 15 of each 4-week cycle (28 days). Substitution of paclitaxel with docetaxel was not allowed.
Vinorelbine 25 mg/m² IV infusion over 10-20 minutes, Days 1, 8, and 15 of each 4-week cycle.
Bevacizumab 10 mg/kg IV infusion, Days 1 and 15 of each 4-week cycle. | 109 |
| Total | 109 |
Baseline characteristics
| Characteristic | Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev |
|---|---|
| Age Continuous | 56.7 Years STANDARD_DEVIATION 12.03 |
| Sex: Female, Male Female | 109 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 103 / 109 |
| serious Total, serious adverse events | 39 / 109 |
Outcome results
Primary
Overall Survival
Overall survival was defined as the time from date of first treatment dose (Day 1) to date of death, across the study phases regardless of the cause of death
Time frame: approximately 505 days (Median Time to Death)
Population: 109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Overall Survival | 505 Days |
Secondary
Number of Participants With Marked Laboratory Abnormalities
The secondary outcome measure was to evaluate the safety profile, including a summary of marked laboratory abnormalities in \>= 5% of patients. n=number of participants with the laboratory measure,Number=number of participants with the abnormality. Laboratory values were flagged as Low(L) or High(H) if they were below the lower limit or above the upper limit of Roche standard reference range, respectively. Marked laboratory abnormalities (flagged as HH and LL) were defined as those values that were outside the Roche marked reference range and showed a clinically relevant change from baseline.
Time frame: until progressive disease or for up to 3 years
Population: 109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Hematocrit (fraction) (n=104); Abnormality: Low | 16 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Hemoglobin (g/L) (n=104); Abnormality: Low | 18 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Platelets (10^9/L) (n=104); Abnormality: Low | 9 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Red blood cells (10¹²/L) (n=104); Abnormality: Low | 15 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | White blood cells (10^9/L)(n=104); Abnormality:Low | 23 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Neutrophils (10^9/L) (n=92); Abnormality: High | 14 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Neutrophils (10^9/L) (n=92); Abnormality: Low | 25 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Prothrombin time (ratio) (n=36); Abnormality: High | 3 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Aspartate transaminase(U/L)(n=104)Abnormality:High | 19 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Alanine transaminase(U/L)(n=104);Abnormality: High | 10 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Alkaline phosphatase(U/L)(n=104);Abnormality: High | 11 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Direct bilirubin (umol/L) (n=78);Abnormality: High | 4 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Albumin (g/L) (n=104); Abnormality: Low | 13 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Total protein (g/L) (n=104); Abnormality: Low | 8 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Chloride (mmol/L) (n=104); Abnormality: Low | 5 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Calcium (mmol/L) (n=104); Abnormality: Low | 10 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Participants With Marked Laboratory Abnormalities | Uric acid (umol/L) (n=94); Abnormality: High | 5 Participants |
Secondary
Number of Subjects With Adverse Events
The secondary outcome measure was to evaluate the safety profile, including a summary of adverse events (AEs) assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Intensity of AEs were graded according to NCI CTCAE version 3.0 on a 5-point scale: Grade 1=Mild Discomfort, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life Threatening/Disabling and Grade 5=Death. An SAE was defined as any experience that suggested a significant hazard,contraindication, side effect, or precaution.
Time frame: Throughout study
Population: 109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Subjects With Adverse Events | At least 1 treatment-related AE | 104 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Subjects With Adverse Events | At least 1 serious adverse event (SAE) | 39 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Subjects With Adverse Events | At least 1 Grade 3 or 4 AE | 82 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Subjects With Adverse Events | At least 1 AE causing withdrawal | 37 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Number of Subjects With Adverse Events | At least 1 adverse event (AE) | 108 Participants |
| First Study Treatment Phase Only | Number of Subjects With Adverse Events | At least 1 AE causing withdrawal | 25 Participants |
| First Study Treatment Phase Only | Number of Subjects With Adverse Events | At least 1 adverse event (AE) | 54 Participants |
| First Study Treatment Phase Only | Number of Subjects With Adverse Events | At least 1 treatment-related AE | 51 Participants |
| First Study Treatment Phase Only | Number of Subjects With Adverse Events | At least 1 Grade 3 or 4 AE | 41 Participants |
| First Study Treatment Phase Only | Number of Subjects With Adverse Events | At least 1 serious adverse event (SAE) | 22 Participants |
Secondary
Premature Withdrawal From Study Due to Adverse Events
The secondary outcome measure was to evaluate the safety profile, including a summary of premature withdrawals due to adverse events occurring in more than 1 patient in either study group, by system organ class.
Time frame: Throughout study
Population: 109 patients (pts) received study drug in the First Study Treatment Phase. 54 pts withdrew prematurely, and 54 pts proceeded to the Second Study Treatment Phase. All 54 pts who proceeded to the Second Study Treatment Phase withdrew during that phase. 1 pt continued treatment in the First Study Treatment Phase and completed 3 years of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Premature Withdrawal From Study Due to Adverse Events | General disorders, administration site conditions | 4 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Premature Withdrawal From Study Due to Adverse Events | Respiratory, thoracic and mediastinal disorders | 2 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Premature Withdrawal From Study Due to Adverse Events | Musculoskeletal and connective tissue disorders | 2 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Premature Withdrawal From Study Due to Adverse Events | Renal and urinary disorders | 2 Participants |
| Capecitabine+Bevacizumab (Bev); Paclitaxel or Vinorelbine +Bev | Premature Withdrawal From Study Due to Adverse Events | All system organ classes | 25 Participants |
| First Study Treatment Phase Only | Premature Withdrawal From Study Due to Adverse Events | Renal and urinary disorders | 2 Participants |
| First Study Treatment Phase Only | Premature Withdrawal From Study Due to Adverse Events | All system organ classes | 37 Participants |
| First Study Treatment Phase Only | Premature Withdrawal From Study Due to Adverse Events | General disorders, administration site conditions | 7 Participants |
| First Study Treatment Phase Only | Premature Withdrawal From Study Due to Adverse Events | Musculoskeletal and connective tissue disorders | 6 Participants |
| First Study Treatment Phase Only | Premature Withdrawal From Study Due to Adverse Events | Respiratory, thoracic and mediastinal disorders | 5 Participants |