Breast Cancer
Conditions
Brief summary
This single arm study will assess the efficacy and safety of combination first-line treatment with docetaxel + Xeloda + Avastin in patients with inflammatory or locally advanced breast cancer. Patients will receive 3-weekly cycles of Avastin (15mg/kg i.v. on day 1 of each cycle), docetaxel (75mg/m2 i.v. on day 1 of each cycle, after Avastin) and Xeloda (2000mg/m2 p.o. on days 1-15 of each cycle). Four cycles of chemotherapy are planned, plus an optional additional two cycles; after chemotherapy patients will be assessed for surgery. The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.
Interventions
DRUGbevacizumab [Avastin]
15mg/kg iv on day 1 of each 3 week cycle
DRUGDocetaxel
75mg/m2 iv on day 1 of each 3 week cycle
DRUGXeloda
2000mg/m2 po on days 1-15 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
* female patients, \>=18 years of age; * HER2-negative, locally advanced (stage II or III) or inflammatory cancer of the breast; * ECOG performance status 0-1.
Exclusion criteria
* metastatic disease (stage IV); * previous treatment for breast cancer; * evidence of CNS metastasis; * current or recent (within 10 days of first dose of Avastin) use of aspirin (\>325mg/day) NSAIDs or full dose anticoagulants for therapeutic purposes; * clinically significant cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Pathological Complete Response (pCR) | At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks) | pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR) | Day 1 of Cycles 1-6 | The percentage of participants with a best overall response of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than \[\<\]10 millimeters \[mm\]). No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Progression-Free Survival | Cycles 1-6 | Progression-free survival was defined as the time from the date of informed consent until the date disease progression was identified, or the date of death from disease progression, whichever occurred first. |
| Overall Survival | Cycles 1-6 | Overall survival was defined as the time from the date of informed consent until the date of death due to any cause. |
| Percentage of Participants Undergoing Breast-Conserving Surgery | Following Cycle 6 | The percentage of participants who were able to undergo breast-conserving surgical procedures (segmentectomy plus lymphadenectomy or quadrantectomy plus lymphadenectomy) rather than non-breast conserving procedures (radical mastectomy or modified-radical mastectomy) following 4 or more treatment cycles. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab+Docetaxel+Capecitabine Participants received bevacizumab 15 mg/kg, IV, on Day 1; docetaxel 75 mg/m\^2, IV, on Day 1; and capecitabine 2000 mg/m\^2, orally, on Days 1-15. This cycle was repeated every 3 weeks for a total of 4 cycles. If all 4 cycles were tolerated, participants then completed an additional 2 cycles, for a maximum of 6 cycles of study treatment. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease course | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Bevacizumab+Docetaxel+Capecitabine |
|---|---|
| Age, Continuous | 51.96 years STANDARD_DEVIATION 11.51 |
| Sex: Female, Male Female | 23 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 | 23 / 23 |
| serious Total, serious adverse events | 2 / 23 |
Outcome results
Primary
Percentage of Participants Achieving Pathological Complete Response (pCR)
pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.
Time frame: At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks)
Population: Evaluable Response (ER) Population: study-eligible participants who completed at least 2 treatment cycles; had lesions evaluated using the same technique at baseline and at least once after receiving the second treatment cycle; and had no major protocol deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Docetaxel+Capecitabine | Percentage of Participants Achieving Pathological Complete Response (pCR) | 0 percentage of participants |
Secondary
Overall Survival
Overall survival was defined as the time from the date of informed consent until the date of death due to any cause.
Time frame: Cycles 1-6
Population: The application of a statistical model for the analysis of disease-free survival is not feasible as the sample size required for statistical analysis could not be recruited within the time established in the protocol and the study was terminated.
Secondary
Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR)
The percentage of participants with a best overall response of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than \[\<\]10 millimeters \[mm\]). No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short aixs was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Day 1 of Cycles 1-6
Population: ER population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Docetaxel+Capecitabine | Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR) | 80 percentage of participants |
Secondary
Percentage of Participants Undergoing Breast-Conserving Surgery
The percentage of participants who were able to undergo breast-conserving surgical procedures (segmentectomy plus lymphadenectomy or quadrantectomy plus lymphadenectomy) rather than non-breast conserving procedures (radical mastectomy or modified-radical mastectomy) following 4 or more treatment cycles.
Time frame: Following Cycle 6
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab+Docetaxel+Capecitabine | Percentage of Participants Undergoing Breast-Conserving Surgery | 26.09 percentage of participants |
Secondary
Progression-Free Survival
Progression-free survival was defined as the time from the date of informed consent until the date disease progression was identified, or the date of death from disease progression, whichever occurred first.
Time frame: Cycles 1-6
Population: The application of a statistical model for the analysis of disease-free survival was not feasible as the sample size required for statistical analysis could not be recruited within the time established in the protocol and the study was terminated.