Breast Cancer, Metastatic Breast Cancer
Conditions
Brief summary
Single-institution phase 2 trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors.
Detailed description
This study will evaluate the time-to-progression (TTP) in patients with metastatic breast cancer, receiving 1st line therapy with bevacizumab in combination with paclitaxel and gemcitabine. Secondary objectives will include response rates and overall survival (OS).
Interventions
DRUGPaclitaxel
Paclitaxel 80 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles
DRUGGemcitabine
Gemcitabine 1000 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles
DRUGBevacizumab
Bevacizumab 10 mg/kg by IV infusion, days 1 and 15 in 28-day cycles
Sponsors
Genentech, Inc.
Eli Lilly and Company
George Albert Fisher
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
* Previously-untreated metastatic breast cancer. May have had prior chest wall irradiation or palliative radiation to bony sites for control of pain or fracture. These sites of disease, however, will not be considered as sites of measurable disease. * Use of bisphosphonates will be permitted. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Granulocyte count ≥ 1500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 8.0 g/dL. * Serum glutamic oxaloacetic transaminase (SGOT) / serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x the institutional upper limit of normal (ULN) if alkaline phosphatase is ≤ ULN or alkaline phosphatase may be up to 4 x ULN if transaminases are ≤ ULN. * Total bilirubin within institutional limits of normal. * Calculated creatinine clearance ≥ 30 mL/min using the formula: Ccr(mL/min) = \[(140-age in years) X (wt in kg) X 0.85 (females)\]/(72 x serum creatinine in mg/dL) * ≥ 18 years of age. * Prior anthracycline treatment in the adjuvant setting or prior chest wall radiation must have left ventricular ejection fraction (LVEF) within the institutional range of normal as assessed by pre-treatment multigated acquisition (MUGA) scan or echocardiogram (ECHO). * All patients must give signed written informed consent. * May have received adjuvant therapy as long as therapy complete \> 12 months from study entry. * Females of childbearing potential must have a negative pregnancy test taken ≤ 2 weeks prior to study enrollment, and must consent to the use of effective contraception during the study period and for 6months thereafter.
Exclusion criteria
* Receiving hormonal therapy * Prior treatment for metastatic disease with cytotoxic agents or inhibitors of epidermal growth factor receptor (EGFR) * Her2NEU-positive breast cancers, by either immunohistochemistry (IHC) score 3+ or fluorescence in situ hybridization (FISH) * Pregnant or lactating. * Patients have had active malignancies other than breast cancer in the past 5 years with the exception of in situ carcinoma of the cervix or nonmelanomatous skin cancer. * Active or unresolved infection. * Pre-existing peripheral neuropathy \> Grade 1. * Prior history of severe hypersensitivity reaction to paclitaxel, gemcitabine, bevacizumab or drugs formulated with polysorbate 80. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study. * Blood pressure of \>150/100 mmHg * Unstable angina * New York Heart Association (NYHA) Grade II or greater congestive heart failure * History of myocardial infarction within 6 months * History of stroke within 6 months * Clinically-significant peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 * Urine protein:creatinine ratio ≥ 1.0 at screening * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * Serious, non-healing wound, ulcer, or bone fracture * Inability to comply with study and/or follow-up procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-Progression (TTP) | 2 years | Time-to-Progression (TTP) was assessed as the time from start of treatment to progression, as observed on radiographic scans and assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for progressive disease (ie, a 5-mm absolute increase of the sum of the longest diameters of the target lesions in addition to a 20% increase in the sum of the target lesions) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates | 24 weeks | The best overall response was recorded for each participant from randomization until disease progression/recurrence, using any increase from the smallest measurements recorded since randomization as the indicator of Progressive Disease (PD). Overall response was determined on the basis of response at the target and non-target lesions, and the appearance of new lesions, as follows. Target Nontarget New Lesions Overall Response * Complete Complete None Overall Complete Response * Complete Incomplete response/ None Overall Partial Response Stable Disease (SD) * Partial Not PD None Overall Partial Response * SD Not PD None Overall Stable Disease * PD Any Yes/No Overall PD * Any PD Yes/No Overall PD * Any Any Yes Overall PD Overall Response Rate (ORR) was assessed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate. |
| Overall Survival (OS), Confirmed | 6 years | Overall Survival (OS) as determined by confirmed date of death. Participants without documentation as either alive or deceased as of 6 years from the start of treatment were considered lost-to-follow-up. |
| Overall Survival (OS), All Participants | 6 years | Overall Survival (OS), based on date of death or last known date alive |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine + Paclitaxel + Bevacizumab * Gemcitabine 1000 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles
* Paclitaxel 80 mg/m2 by IV infusion, days 1, 8, and 15 in 28-day cycles
* Bevacizumab 10 mg/kg by IV infusion, days 1 and 15 in 28-day cycles | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 2 Years From Start of Treatment | Lost to Follow up | 1 |
| 2 Years From Start of Treatment | Not Eligible | 3 |
| 2 Years From Start of Treatment | Withdrawal by Subject | 1 |
| Survival Follow-up up to 6 Years | Lost to Follow-up | 10 |
Baseline characteristics
| Characteristic | Gemcitabine + Paclitaxel + Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 31 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 | 26 / 28 |
| serious Total, serious adverse events | 18 / 26 |
Outcome results
Primary
Time-to-Progression (TTP)
Time-to-Progression (TTP) was assessed as the time from start of treatment to progression, as observed on radiographic scans and assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria for progressive disease (ie, a 5-mm absolute increase of the sum of the longest diameters of the target lesions in addition to a 20% increase in the sum of the target lesions)
Time frame: 2 years
Population: Disease progression was documented for 9 participants.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Bevacizumab + Gemcitabine + Paclitaxel | Time-to-Progression (TTP) | 8.9 months | Standard Deviation 5.9 |
Secondary
Overall Survival (OS), All Participants
Overall Survival (OS), based on date of death or last known date alive
Time frame: 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Gemcitabine + Paclitaxel | Overall Survival (OS), All Participants | 14.8 months |
Secondary
Overall Survival (OS), Confirmed
Overall Survival (OS) as determined by confirmed date of death. Participants without documentation as either alive or deceased as of 6 years from the start of treatment were considered lost-to-follow-up.
Time frame: 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + Gemcitabine + Paclitaxel | Overall Survival (OS), Confirmed | 33.7 months |
Secondary
Response Rates
The best overall response was recorded for each participant from randomization until disease progression/recurrence, using any increase from the smallest measurements recorded since randomization as the indicator of Progressive Disease (PD). Overall response was determined on the basis of response at the target and non-target lesions, and the appearance of new lesions, as follows. Target Nontarget New Lesions Overall Response * Complete Complete None Overall Complete Response * Complete Incomplete response/ None Overall Partial Response Stable Disease (SD) * Partial Not PD None Overall Partial Response * SD Not PD None Overall Stable Disease * PD Any Yes/No Overall PD * Any PD Yes/No Overall PD * Any Any Yes Overall PD Overall Response Rate (ORR) was assessed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate.
Time frame: 24 weeks
Population: Although 24 participants completed treatment, only 13 were evaluable for treatment effect.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab + Gemcitabine + Paclitaxel | Response Rates | Partial Response (PR) | 4 Participants |
| Bevacizumab + Gemcitabine + Paclitaxel | Response Rates | Stable Disease (SD) | 1 Participants |
| Bevacizumab + Gemcitabine + Paclitaxel | Response Rates | Progressive Disease (PD) | 7 Participants |
| Bevacizumab + Gemcitabine + Paclitaxel | Response Rates | Overall Response Rate (ORR) | 5 Participants |
| Bevacizumab + Gemcitabine + Paclitaxel | Response Rates | Complete Response (CR) | 1 Participants |