Metastatic Breast Cancer
Conditions
Brief summary
Prior clinical trials involving bevacizumab and sorafenib have demonstrated single agent activity in previously treated advanced breast cancer. This trial will test combined VEGF inhibition with sorafenib and bevacizumab in less heavily pre-treated patients with advanced breast cancer.
Detailed description
OUTLINE: This is a multi-center study. Sorafenib 200mg po daily Bevacizumab 5mg/kg every other week 1 Cycle = 4 weeks Imaging every third cycle Acceptable toxicity and non-PD = Protocol therapy will continue Un-acceptable toxicity or PD = Protocol therapy will be discontinued ECOG Performance Status 0-1 Life Expectancy: at least 12 weeks Hematopoietic: * Platelets \> 100 K/mm3 * Absolute neutrophil count (ANC) \> 1.5 K/mm3 * Hemoglobin \> 10 g/dL Hepatic: * Total Bilirubin \< 1.5 x ULN * Aspartate aminotransferase (AST, SGOT) \< 2 x ULN (up to 5 x ULN in patients with known liver involvement) Renal: * Creatinine \< 1.5 x ULN * No proteinuria as demonstrated by either Urine protein:creatinine (UPC) ratio \< 1.0 or Urine dipstick for proteinuria \< 2+ Cardiovascular: * No known myocardial infarction, unstable angina, \> grade II New York Heart Association (NYHA) classification, congestive heart failure, uncontrolled hypertension defined as SBP \>150 or DBP \>100, \> grade II peripheral vascular disease or significant vascular disease (e.g. aortic aneurysm, aortic dissection) within 12 months prior to being registered for protocol therapy. * No uncontrolled or clinically significant arrhythmia. NOTE: Controlled atrial fibrillation is allowed. * LVEF ≥ LLN by MUGA or ECHO as obtained within 28 days prior to being registered for protocol therapy. Pulmonary: * No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within 28 days prior to being registered for protocol therapy.
Interventions
DRUGSorafenib
Sorafenib 200mg po daily
DRUGBevacizumab
Bevacizumab 5mg/kg every other week 1 Cycle = 4 weeks
OTHERImaging
Imaging every third cycle
Sponsors
Genentech, Inc.
Bayer
Amgen
Hoosier Cancer Research Network
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
* Histologic or cytologic diagnosis of breast cancer with evidence of metastatic disease. NOTE: Patients with Her-2 positive (3+ by IHC or gene amplification by FISH) are eligible only if they have had prior trastuzumab therapy. * Must have measurable or non-measurable lesions as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). * Two or fewer prior chemotherapy regimens in any disease setting. NOTE: All adjuvant and neoadjuvant chemotherapy will be considered one regimen. NOTE: Prior hormonal therapy for metastatic disease is allowed. NOTE: Prior radiation therapy is allowed as long as the irradiated area is not the only source of evaluable disease. * Age \> 18 years at the time of consent. * Written informed consent and HIPAA authorization for release of personal health information. * Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation. * Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. * Ability to comply with study and/or follow-up procedures.
Exclusion criteria
* No prior therapy with bevacizumab, sorafenib or any other known VEGF inhibitors. * No known hypersensitivity to any component of the study drugs. * No other forms of cancer therapy including radiation, chemotherapy and hormonal therapy within 21 days prior to being registered for protocol therapy. * No history or radiologic evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptominigeal involvement. A head CT or MRI must be obtained within 28 days prior to being registered for protocol therapy. * No other participation in another clinical drug study within 28 days prior to being registered for protocol therapy. * No known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C * No major surgical procedure within 28 days prior to being registered for protocol therapy or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device and breast biopsy will not be considered major surgery. * No minor surgical procedure within 7 days prior to being registered for protocol therapy. * No known history of cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage. * No known history of ischemic bowel. * No known history of deep venous thrombosis or pulmonary embolism. * No history of hypertensive crisis or hypertensive encephalopathy. * No non-healing wound or fracture. * No active infection requiring parenteral antibiotics. * No other hemorrhage/bleeding event ≥ CTCAE grade 3 within 28 days prior to being registered for protocol therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From the start of the treatment until the criteria for disease progression is met (or death occurs) maximum of 24 months | The primary objective was to assess the Progression-Free Survival of sorafenib combined with bevacizumab in patients with metastatic breast cancer. Progression is defined by RECIST as a 20% increase in the sum of the longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion. |
Secondary
| Measure | Time frame |
|---|---|
| Assess the Clinical Benefit Response: the Proportion of Patients With Clinical Benefit (CR+PR+SD > 6 Months Duration) Will be Assessed at the Completion of the Study. | 6 months |
| Assess the Overall Response Rate. | 24 months |
| Determine the Adverse Event Profile of Sorafenib Combined With Bevacizumab in This Patient Population. | 24 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm A Sorafenib 200mg po daily, Bevacizumab 5mg/kg every other week, 1 Cycle = 4 weeks. Imaging every third cycle | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
Baseline characteristics
| Characteristic | Single Arm A |
|---|---|
| Age, Continuous | 56 years |
| Breast Cancer Subtype ER-/PR-/HER2- | 8 participants |
| Breast Cancer Subtype ER-/PR-/HER2+ | 1 participants |
| Breast Cancer Subtype ER+/PR-/HER2- | 4 participants |
| Breast Cancer Subtype ER+/PR+/HER2- | 3 participants |
| Breast Cancer Subtype ER+/PR+/HER2 unknown | 2 participants |
| ECOG Performance Status ECOG = 0 | 13 participants |
| ECOG Performance Status ECOG = 1 | 5 participants |
| Prior Chemotherapy Regimens Prior Chemotherapy Regimens - 0 | 1 participants |
| Prior Chemotherapy Regimens Prior Chemotherapy Regimens 1-2 | 17 participants |
| Prior Hormone Therapy No Prior Hormone Therapy | 9 participants |
| Prior Hormone Therapy Prior Hormone Therapy | 9 participants |
| Prior Radiation Therapy No Prior Radiation Therapy | 7 participants |
| Prior Radiation Therapy Prior Radiation Therapy | 11 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 4 / 18 |
Outcome results
Primary
Progression-Free Survival
The primary objective was to assess the Progression-Free Survival of sorafenib combined with bevacizumab in patients with metastatic breast cancer. Progression is defined by RECIST as a 20% increase in the sum of the longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion.
Time frame: From the start of the treatment until the criteria for disease progression is met (or death occurs) maximum of 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm A | Progression-Free Survival | 2.8 months |
Secondary
Assess the Clinical Benefit Response: the Proportion of Patients With Clinical Benefit (CR+PR+SD > 6 Months Duration) Will be Assessed at the Completion of the Study.
Time frame: 6 months
Population: Data for this secondary objective was not collected or analyzed
Secondary
Assess the Overall Response Rate.
Time frame: 24 months
Population: Data for this secondary objective was not collected or analyzed.
Secondary
Determine the Adverse Event Profile of Sorafenib Combined With Bevacizumab in This Patient Population.
Time frame: 24 months
Population: Data for this secondary objective was not collected or analyzed.