Locally Advanced Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
Breast Neoplasm
Brief summary
To determine how long Gemcitabine and Bevacizumab will stop the cancer from growing in patients with advanced breast cancer.
Interventions
DRUGGemcitabine
Gemcitabine 2500 mg/m\^2 IV over 30 minutes given on Day 1 q 14 days prior to bevacizumab until PD or unacceptable toxicity.
DRUGBevacizumab
Bevacizumab 10 mg/kg IV over 90 minutes at Cycle 1; infusion time may have been decreased for subsequent cycles. (For example, if the first infusion was tolerated without an infusion-associated adverse event \[AE\], the second infusion was delivered over 60 minutes. If the 60-minute infusion was well tolerated, all subsequent infusions were delivered over 30 minutes.) Bevacizumab 10 mg/kg initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Sponsors
Genentech, Inc.
Eli Lilly and Company
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
* Must be female and greater than or equal to 18 yrs of age * Participants must have confirmed cancer with measurable or evaluable, locally recurrent or metastatic disease. * Participants must have received a taxane as neo-adjuvant and/or adjuvant therapy * Participants may have received prior hormone therapy for locally recurrent or metastatic disease
Exclusion criteria
* Participants with breast cancer overexpressing Human Epidermal growth factor Receptor 2 (HER2) gene amplification * Prior chemotherapy or targeted therapy for metastatic breast cancer * Prior treatment with gemcitabine, trastuzumab, lapatinib or bevacizumab in any setting * History of, or active brain mets * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment, or anticipation of need for major surgical procedure during course of study * Prior history of high blood pressure crisis * Have a serious, nonhealing wound, ulcer, or bone fracture
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Time | Baseline to measured PD or death from any cause. Tumor assessments were performed every 8 weeks during therapy and every 2 months during post-therapy until documented PD (up to 34 months). | PFS was measured from date of first dose to first date of progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had PD as of the data inclusion cut-off date for a particular analysis, PFS duration was censored for that analysis at the date of the participant's last progression-free tumor assessment before that cut-off date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response Rate (ORR) | Baseline to measured PD. Tumor assessments were performed every 8 weeks (q 8 weeks) during therapy and q 2 months during post-therapy until documented PD (up to 34 months). | Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: complete response (CR)=disappearance of all target lesions; partial response (PR)=30% decrease in sum of longest diameter of target lesions; progressive disease (PD)=20% increase in sum of longest diameter of target lesions; stable disease=small changes that do not meet above criteria. ORR=proportion of participants who achieved a confirmed best response of CR or PR (responders). ORR=number of participants with CR or PR /number of participants qualified for tumor response analysis (per protocol population). |
| Number of Participants With Adverse Events (AEs); Pharmacology Toxicities | Baseline, every cycle (every 14 days) up to 34 months | A listing of serious adverse events (SAEs) and other non-serious AEs is located in the Reported Adverse Event module. |
| 1-Year Overall Survival (OS) Rate | Baseline to death from any cause, 1 year | OS was measured from the date of first dose to the date of death from any cause. For each participant who was not known to have died as of the data inclusion cut-off date for a particular analysis, OS duration was censored for that analysis at the date of participant's last study contact prior to that cut-off date. The 1-year survival rate (percentage of participants who were alive at 1 year) was estimated from OS data. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg Gemcitabine 2500 milligrams per square meter (mg/m\^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity.
Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 10 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 10 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg |
|---|---|
| Age Continuous | 55.2 years STANDARD_DEVIATION 11.66 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 28 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 24 participants |
| Estrogen Receptor (ER) Status ER- | 19 participants |
| Estrogen Receptor (ER) Status ER+ | 33 participants |
| Human Epidermal Growth Factor Receptor 2 (HER2/neu) HER2/neu- | 52 participants |
| Human Epidermal Growth Factor Receptor 2 (HER2/neu) HER2/neu+ | 0 participants |
| Progesterone Receptor (PR) Status PR- | 22 participants |
| Progesterone Receptor (PR) Status PR+ | 30 participants |
| Race/Ethnicity, Customized African descent | 11 participants |
| Race/Ethnicity, Customized Caucasian | 41 participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 52 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 | 51 / 52 |
| serious Total, serious adverse events | 18 / 52 |
Outcome results
Primary
Progression Free Survival (PFS) Time
PFS was measured from date of first dose to first date of progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had PD as of the data inclusion cut-off date for a particular analysis, PFS duration was censored for that analysis at the date of the participant's last progression-free tumor assessment before that cut-off date.
Time frame: Baseline to measured PD or death from any cause. Tumor assessments were performed every 8 weeks during therapy and every 2 months during post-therapy until documented PD (up to 34 months).
Population: The intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug. Participants with events=41; censored participants=11.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg | Progression Free Survival (PFS) Time | 4.80 months |
Secondary
1-Year Overall Survival (OS) Rate
OS was measured from the date of first dose to the date of death from any cause. For each participant who was not known to have died as of the data inclusion cut-off date for a particular analysis, OS duration was censored for that analysis at the date of participant's last study contact prior to that cut-off date. The 1-year survival rate (percentage of participants who were alive at 1 year) was estimated from OS data.
Time frame: Baseline to death from any cause, 1 year
Population: The intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug. Participants with events=25; censored participants=27.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg | 1-Year Overall Survival (OS) Rate | 68.68 percentage of participants |
Secondary
Number of Participants With Adverse Events (AEs); Pharmacology Toxicities
A listing of serious adverse events (SAEs) and other non-serious AEs is located in the Reported Adverse Event module.
Time frame: Baseline, every cycle (every 14 days) up to 34 months
Population: The safety population was the treated population and included all participants who received at least 1 dose of study therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg | Number of Participants With Adverse Events (AEs); Pharmacology Toxicities | SAEs | 18 participants |
| Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg | Number of Participants With Adverse Events (AEs); Pharmacology Toxicities | Other non-serious AEs | 51 participants |
Secondary
Overall Tumor Response Rate (ORR)
Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: complete response (CR)=disappearance of all target lesions; partial response (PR)=30% decrease in sum of longest diameter of target lesions; progressive disease (PD)=20% increase in sum of longest diameter of target lesions; stable disease=small changes that do not meet above criteria. ORR=proportion of participants who achieved a confirmed best response of CR or PR (responders). ORR=number of participants with CR or PR /number of participants qualified for tumor response analysis (per protocol population).
Time frame: Baseline to measured PD. Tumor assessments were performed every 8 weeks (q 8 weeks) during therapy and q 2 months during post-therapy until documented PD (up to 34 months).
Population: The per protocol (PP) population included all intent-to-treat (ITT) participants who met the following criteria: histological or cytological diagnosis of breast cancer; presence of measurable disease at baseline per RECIST criteria; had at least 1 dose of study drug; no current systemic anti-tumor treatment other than protocol-specified therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg | Overall Tumor Response Rate (ORR) | 0.214 proportion of responders |