Breast Cancer
Conditions
Brief summary
This single arm study will assess the efficacy and safety of sequential neoadjuvant chemotherapy and bevacizumab (Avastin), before surgery and/or radiotherapy, in participants with inflammatory or locally advanced operable breast cancer. Participants will receive 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC), followed by paclitaxel, given concomitantly with bevacizumab. The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.
Interventions
DRUG5-fluorouracil
600 milligrams per meter squared (mg/m\^2) as an intravenous (i.v.) bolus over ≤15 minutes every 3 weeks for 4 cycles.
DRUGEpidoxorubicin
90 mg/m\^2 as an i.v. infusion over 1 hour every 3 weeks for 4 cycles.
DRUGCyclophosphamide
600 mg/m\^2 as an i.v. infusion over 1 hour every 3 weeks for 4 cycles.
DRUGPaclitaxel
Paclitaxel was administered at 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks.
BIOLOGICALBevacizumab
Bevacizumab was administered at 10 milligrams per kilogram (mg/kg) i.v. every 2 weeks for 6 cycles.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
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 participants, \>=18 years of age; * stage III, or inflammatory breast cancer; * estrogen receptor/progesterone receptor (ER/PgR) positive or negative and human epidermal growth factor receptor 2 (HER-2) negative; * normal left ventricular ejection fraction (LVEF).
Exclusion criteria
* previous chemotherapy/endocrine therapy; * evidence of distant metastatic disease; * other primary tumors in last 5 years (except for adequately treated cancer in situ of the cervix, or basal cell skin cancer); * chronic daily treatment with \>325 milligram per day (mg/day) aspirin, or \>75mg/day clopidogrel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pathological Complete Response Following Principle Investigator Review | Up to 7.5 years | Pathological complete response was defined as absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 7.5 years | Objective response rate was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions. |
| Percentage of Participants With Breast-Conserving Surgery | Up to 7.5 years | Rate of breast conversing surgery is defined as percentage of participants who achieved breast conversing surgery out of the ITT population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant treatment. |
| Percentage of Participants With Disease-Free Interval | Months 12, 24, 36, 48, and 60 | Disease-free interval was defined as the time from enrollment until recurrence of tumor or death from any cause, and was estimated using the Kaplan-Meier method. The percentage of participants without events at Months 12, 24, 36, 48, and 60 is presented. |
| Overall Survival | Up to 7.5 years | Overall survival was defined as the time from enrollment of participant to death from any cause. |
| Percentage of Participants Experiencing Any Adverse Event | Up to 7.5 years | An adverse event was defined as 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. |
Countries
Italy
Participant flow
Pre-assignment details
56 participants were enrolled in 8 centers in Italy.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months.
FEC: 5-Fluorouracil 600 mg/m\^2 i.v. bolus over ≤15 min; epirubicin 90 mg/m\^2 i.v. infusion over 1 hour; cyclophosphamide 600 mg/m\^2 i.v. infusion over 1 hour every 3 weeks for 4 cycles.
Paclitaxel: 80 mg/m\^2 i.v. over 1 hour weekly for 12 weeks.
Bevacizumab: 10 mg/kg i.v. every 2 weeks for 6 cycles. | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Did Not Attend Cycle 6 Hospital Visit | 1 |
| Overall Study | Disease Progression | 1 |
| Overall Study | Premature Surgery-Investigator Decision | 1 |
| Overall Study | Withdrew Consent | 1 |
Baseline characteristics
| Characteristic | Bevacizumab |
|---|---|
| Age, Continuous | 50.00 years STANDARD_DEVIATION 9.279 |
| Sex: Female, Male Female | 56 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 | 54 / 54 |
| serious Total, serious adverse events | 8 / 54 |
Outcome results
Primary
Percentage of Participants With Pathological Complete Response Following Principle Investigator Review
Pathological complete response was defined as absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy.
Time frame: Up to 7.5 years
Population: Intention-to-Treat (ITT) population, defined as all participants that were included in the trial and underwent surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants With Pathological Complete Response Following Principle Investigator Review | 23.2 percentage of participants |
Secondary
Objective Response Rate
Objective response rate was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions.
Time frame: Up to 7.5 years
Population: ITT population, defined as all participants that were included in the trial and underwent surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Objective Response Rate | 59.0 percentage of participants |
Secondary
Overall Survival
Overall survival was defined as the time from enrollment of participant to death from any cause.
Time frame: Up to 7.5 years
Population: Data for the outcome measure was not collected.
Secondary
Percentage of Participants Experiencing Any Adverse Event
An adverse event was defined as 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.
Time frame: Up to 7.5 years
Population: Safety population, defined as all participants who received at least one infusion of Bevacizumab.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab | Percentage of Participants Experiencing Any Adverse Event | 100.0 percentage of participants |
Secondary
Percentage of Participants With Breast-Conserving Surgery
Rate of breast conversing surgery is defined as percentage of participants who achieved breast conversing surgery out of the ITT population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant treatment.
Time frame: Up to 7.5 years
Population: ITT population, defined as all participants that were included in the trial and underwent surgery.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Breast-Conserving Surgery | Breast-conserving | 17.0 percentage of participants |
| Bevacizumab | Percentage of Participants With Breast-Conserving Surgery | Breast-conserving Plus Axillary Dissection | 13.2 percentage of participants |
Secondary
Percentage of Participants With Disease-Free Interval
Disease-free interval was defined as the time from enrollment until recurrence of tumor or death from any cause, and was estimated using the Kaplan-Meier method. The percentage of participants without events at Months 12, 24, 36, 48, and 60 is presented.
Time frame: Months 12, 24, 36, 48, and 60
Population: ITT population, defined as all participants that were included in the trial and underwent surgery. Here, number of participants analyzed signifies those participants who were evaluable for the outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab | Percentage of Participants With Disease-Free Interval | 12 Months | 92.2 percentage of participants |
| Bevacizumab | Percentage of Participants With Disease-Free Interval | 24 Months | 84.3 percentage of participants |
| Bevacizumab | Percentage of Participants With Disease-Free Interval | 36 Months | 80.4 percentage of participants |
| Bevacizumab | Percentage of Participants With Disease-Free Interval | 48 Months | 76.5 percentage of participants |
| Bevacizumab | Percentage of Participants With Disease-Free Interval | 60 Months | 76.5 percentage of participants |