Metastatic Breast Cancer
Conditions
Keywords
Metastatic breast cancer, Abraxane, Bevacizumab
Brief summary
The purpose of this study is to evaluate the safety and tolerability of weekly ABI-007 in combination with bevacizumab. The evaluation of progression-free survival of weekly ABI-007 in combination with bevacizumab for patients with previously untreated advanced/metastatic breast cancer.
Interventions
DRUGABI-007
125 mg/m\^2 of ABI-007 administered by intravenously (IV) over 30 minutes on days 1, 8 and 15 of each 28 day cycle.
DRUGBevacizumab
Bevacizumab administered once every 2 weeks (10 mg/kg) by IV infusion after ABI-007 has been given. The first dose is one Day 1, cycle 1.
Sponsors
Celgene
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
* Pathologically confirmed adenocarcinoma of the breast. * Stage IV disease. * Measurable disease (defined as the presence of at least one lesion that can be accurately measured in at least one dimension with longest diameter greater or = 1.0 cm with spiral computed tomography (CT) scan). * Patients must not be a candidate for Herceptin therapy (i.e., patients with HER-2 positive disease (gene amplification by fluorescence in situ hybridization (FISH) or 3 + overexpression by ICH) and patients with unknown HER-2 status are ineligible unless the treating physicians has determined that Herceptin-based therapy would be inappropriate or not indicated). * For subjects with prior anthracycline exposure, normal cardiac function including a baseline left ventricle ejection fraction \>50% or above institution's lower limit of normal and a normal electrocardiogram (ECG) (as assessed by the investigator). * At least 2 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease within the radiation portal. * International Normalized Ratio (INR) \< 1.5 and activated partial thromboplastin time within normal limits (APTT WNL). * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Female \> 18 years of age. * Patients have the following blood counts at Baseline: absolute neutrophil count (ANC) greater or equal to 1.5 x 10\^9 cells/L; platelets greater or equal 100 x 10\^9 cells/L; hemoglobin (Hgb) greater or equal to 9g/dL. * Patients have the following blood chemistry levels at Baseline: aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT) less than or equal 2.5x upper limit of normal (ULN) range (less than or equal 5x ULN if patient has known liver metastases); total bilirubin greater than or equal to ULN; creatinine greater or equal to 1.5mg/dL. * if female of childbearing potential, pregnancy test is negative within 72 hours of first dose of study drug. * if fertile, the patient agrees to use an effective method to avoid pregnancy for the duration of the study. * Informed consent has been obtained.
Exclusion criteria
* No prior chemotherapy for metastatic or locally recurrent disease is allowed. * Prio neo-adjuvant chemotherapy is allowed, and patients must have recovered from the acute toxicity of such therapies. * if a taxane was part of the adjuvant regimen, at least 12 months must have elapsed between the last dose of the taxane and the date of diagnosis of metastatic disease. * if a non-taxane-based adjuvant therapy was administered, at least six months must have elapsed between the last dose of the non- taxane-containing chemotherapy and the date of diagnosis of metastatic disease. * Concurrent immunotherapy or hormonal therapy. * Parenchymal brain metastases, including leptomeningeal involvement. * Uncontrolled hypertension (defined as blood pressure of \> 150/100 mmHg) * NYHA Grade 2 or greater congestive heart failure * History of coagulopathy, bleeding diathesis, therapeutic anticoagulation other than low dose or chronic ASA greater than or equal to 325 mg per day. Low dose coumadin for anticoagulation of venous access device or low dose molecular weight heparin (LMWH)for deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are allowed, but are best avoided if the treating physician feels it is safe to do so. * Urine protein:creatinine ratio less than or equal to 1.0 at screening. * No history of cerebrovascular accident within six months of study entry. * Active symptomatic peripheral vascular disease (e.g. aortic aneurysm, claudication) within six months of study entry. * Uncontrolled or severe cardiovascular disease including myocardial infarction or unstable angina within six months of study entry. * No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal process within six months of study entry. * No serious non-healing wound, ulcer, or bone fracture * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose, or anticipation of need for major surgical procedure during the course of the study. No minor surgical procedure within seven days of study entry. Serious intercurrent medical or psychiatric illness, including serious active infection. * History of other malignancy within the last 5 years which could affect the diagnosis or assessment of breast cancer. * Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study. * Pregnant or nursing women. * Patients with current sensory neuropathy of \> Grade 1 will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | up to 25 months | Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug. |
| Kaplan-Meier Estimates for Progression-free Survival | up to 39 months | Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first. Patients who do not have disease progression or have not died at the end of follow-up were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Response Evaluation Criteria in Solid Tumors (RECIST) defines progressive disease (PD) as a \>= 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | up to 39 months | Objective response is complete response (CR) + partial response (PR). RECIST defines overall response of CR as the disappearance of all target and non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. Overall response of PR is defined as \>= 30% decrease from baseline in the sum of the longest diameters of target lesions and no progression of non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing and no appearance of new lesions. The objective response is determined by combining the response of target and non-target lesions and the appearance of new lesion(s) or not together. |
| Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | up to 39 months | Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). RECIST defines SD as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease and no new lesions. Definitions for CR and PR can be found in outcome #3. |
| Kaplan-Meier Estimate for Duration of Response | up to 39 months | Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease is defined in outcome #2. Complete response (CR) and partial response (PR) are defined in outcome #3. |
| Kaplan-Meier Estimates for Participant Survival | up to 39 months | Participant survival is the time from the first dose of study drug to patient death from any cause. Patients that did not die were censored at the last known time the patient was alive. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABI-007 Plus Bevacizumab ABI-007 is administered on days 1, 8 and 15 at 125 mg/m\^2 and bevacizumab is administered on day 1 and 15 at 10 mg/kg of each 28 day cycle. Treatment continues until disease progression or intolerable toxicity. If a patient develops intolerable toxicity to only one of the drugs, the other drug may be continued as single agent therapy in the absence of progression, as long as the treating physician feels this is in the best interests of the patient. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Other | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Unacceptable toxicity | 15 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | ABI-007 Plus Bevacizumab |
|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 11.03 |
| Dominant Current Site of Metastasis/Relapse Non Visceral | 1 participants |
| Dominant Current Site of Metastasis/Relapse Visceral | 49 participants |
| Eastern Cooperative Oncology Group (ECOG) status 0 (Fully Active) | 23 participants |
| Eastern Cooperative Oncology Group (ECOG) status 1 (Restrictive but Ambulatory) | 25 participants |
| Eastern Cooperative Oncology Group (ECOG) status 2 (Ambulatory but Unable to Work) | 2 participants |
| Eastern Cooperative Oncology Group (ECOG) status 3 (Limited Self-Care) | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) status 4 (Completely Disabled) | 0 participants |
| Menopausal status Post-menopausal | 43 participants |
| Menopausal status Pre-menopausal | 7 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White, Hispanic or Latino | 7 participants |
| Race/Ethnicity, Customized White, Non-Hispanic and Non-Latino | 40 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 0 Participants |
| Time from First Documented Metastasis/Relapse to Study Entry | 1.01 years STANDARD_DEVIATION 3.123 |
| Weight | 74.52 kilograms STANDARD_DEVIATION 15.43 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 50 |
| serious Total, serious adverse events | 13 / 50 |
Outcome results
Primary
Kaplan-Meier Estimates for Progression-free Survival
Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first. Patients who do not have disease progression or have not died at the end of follow-up were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Response Evaluation Criteria in Solid Tumors (RECIST) defines progressive disease (PD) as a \>= 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time frame: up to 39 months
Population: Treated population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABI-007 Plus Bevacizumab | Kaplan-Meier Estimates for Progression-free Survival | 8.0 months |
Primary
Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
Count of study participants who had at least one treatment-emergent adverse event (TEAE) defined as any adverse event that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug.
Time frame: up to 25 months
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABI-007 Plus Bevacizumab | Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 50 participants |
Secondary
Kaplan-Meier Estimate for Duration of Response
Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progressive disease is defined in outcome #2. Complete response (CR) and partial response (PR) are defined in outcome #3.
Time frame: up to 39 months
Population: Treated population of participants who had a response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABI-007 Plus Bevacizumab | Kaplan-Meier Estimate for Duration of Response | 10.3 months |
Secondary
Kaplan-Meier Estimates for Participant Survival
Participant survival is the time from the first dose of study drug to patient death from any cause. Patients that did not die were censored at the last known time the patient was alive.
Time frame: up to 39 months
Population: Treated population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABI-007 Plus Bevacizumab | Kaplan-Meier Estimates for Participant Survival | 17.1 months |
Secondary
Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Objective response is complete response (CR) + partial response (PR). RECIST defines overall response of CR as the disappearance of all target and non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. Overall response of PR is defined as \>= 30% decrease from baseline in the sum of the longest diameters of target lesions and no progression of non-target lesions and no appearance of new lesions, confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing and no appearance of new lesions. The objective response is determined by combining the response of target and non-target lesions and the appearance of new lesion(s) or not together.
Time frame: up to 39 months
Population: Treated population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABI-007 Plus Bevacizumab | Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Overall response (CR + PR) | 30 percentage of participants |
| ABI-007 Plus Bevacizumab | Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Complete response (CR) | 0 percentage of participants |
| ABI-007 Plus Bevacizumab | Percentage of Participants With Objective Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Partial response (PR) | 30 percentage of participants |
Secondary
Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). RECIST defines SD as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease and no new lesions. Definitions for CR and PR can be found in outcome #3.
Time frame: up to 39 months
Population: Treated population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABI-007 Plus Bevacizumab | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Complete response (CR) | 0 percentage of participants |
| ABI-007 Plus Bevacizumab | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | CR + PR + SD>=16 weeks | 50 percentage of participants |
| ABI-007 Plus Bevacizumab | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Partial response (PR) | 30 percentage of participants |
| ABI-007 Plus Bevacizumab | Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST) | Stable disease >=16 weeks (SD>=16 weeks) | 20 percentage of participants |