Metastatic Breast Cancer
Conditions
Brief summary
The purpose of this study is to determine the progression free survival (PFS) of metastatic ER, PR and HER2/neu negative breast cancers to the combination of carboplatin and bevacizumab (Avastin®) therapy.
Interventions
DRUGcarboplatin
AUC 6 in 250mL saline IV over 30 minutes
DRUGbevacizumab
15mg/kg in 100mL saline IV over 60 - 90 minutes
Sponsors
Genentech, Inc.
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have pathologically confirmed ER, PR and HER2/neu negative (FISH ratio of \<2.0 or IHC \<1+) metastatic breast cancer. Locally advanced or recurrent disease is also eligible. * Patients must have measurable disease * Patients must not have received prior chemotherapy for metastatic breast cancer (not including adjuvant therapy). Patients should be \> 4 weeks from their most recent chemotherapy or radiation therapy treatment. * Age \>18 years * ECOG performance status \<1 (Karnofsky \>80%). * Patients must have normal organ and marrow function as defined below: * absolute neutrophil count \>1,500/uL * platelets \>100,000/uL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) \<2.5X institutional upper limit of normal * creatinine within normal institutional limits OR creatinine clearance\>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * PT INR \< 1.5 (Unless patient is on anticoagulation) * urine protein \<1+ * Tissue from the primary tumor must be available for correlative studies * Women of child-bearing potential must agree to use adequate contraception * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Patients who have had prior therapy with platinum agents or a VEGF inhibitor are not eligible. * Patients may not be receiving any other investigational agents. * Patients with known brain metastases will be excluded * Patients may have had prior radiation therapy, provided the patient has measurable disease and there has been clear progression since the completion of radiation therapy. Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to therapy administered more than 4 weeks earlier will be excluded. * Patients with significant cardiac dysfunction will be excluded * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study, breastfeeding should be discontinued. * HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with carboplatin or the other agents administered during the study. * Patients with evidence of bleeding diathesis or coagulopathy. * Patients with inadequately controlled hypertension will be excluded * Patients who have had a stroke or TIA within 6 months of registration will be excluded. * Patients with a history of hypertensive crisis or hypertensive encephalopathy will be excluded. * Patients with a history of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months of registration. * Patient with history of serious non-healing wound, ulcer or bone fracture. * Patients with major surgery, open biopsy, or significant traumatic injury within 28 days of registration or anticipated need for surgery during course of study treatment. * Patients with a history core biopsy or other minor surgery, excluding venous access device (VAD) placement, within 7 days of registration. * Patients with active second malignancy. * Known hypersensitivity to any component of bevacizumab (Avastin®). * Peripheral neuropathy \> Grade 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 5 years | Progression is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI 92(3):205-216, 2000\], as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Up to 5 years | Response is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI 92(3):205-216, 2000\]: Complete Response (CR), Disappearance of all target lesions or disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. |
| Duration of Response | Up to 5 years | — |
| Correlation of Response to BRCA1 Methylation Status | Up to 5 years | The methylation status of the tumor is defined using Methylation Specific polymerase chain reaction and/or pyrosequencing. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin + Avastin Carboplatin in 250mL saline IV over 30 minutes and Avastin (Bevacizumab) 15mg/kg in 100mL saline IV over 60 - 90 minutes | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | The study was terminated | 5 |
Baseline characteristics
| Characteristic | Carboplatin + Avastin |
|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 11 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 | 9 / 11 |
| serious Total, serious adverse events | 1 / 11 |
Outcome results
Primary
Progression Free Survival
Progression is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI 92(3):205-216, 2000\], as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Up to 5 years
Population: This study has been terminated due to poor accrual.
Secondary
Correlation of Response to BRCA1 Methylation Status
The methylation status of the tumor is defined using Methylation Specific polymerase chain reaction and/or pyrosequencing.
Time frame: Up to 5 years
Population: This study has been terminated due to poor accrual.
Secondary
Duration of Response
Time frame: Up to 5 years
Population: This study has been terminated due to poor accrual.
Secondary
Response Rate
Response is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI 92(3):205-216, 2000\]: Complete Response (CR), Disappearance of all target lesions or disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
Time frame: Up to 5 years
Population: This study has been terminated due to poor accrual.