- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01004172
Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases
Phase II Trial of Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, United States, 02115
- Beth Israel Deaconess Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed invasive breast cancer, with metastatic disease. patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study
- Measurable disease. Patients must have measurable CNS disease, defined as at least one parenchymal brain lesion that can be accurately measured in at least one dimension with longest dimension >/= 10mm by local radiology review
- New or progressive CNS lesions, as assessed by the patient's treating physician
- No increase in corticosteroid dose in the week prior to the baseline brain MRI
- 18 years of age or older
- Life expectancy of greater than 12 weeks
- Eastern Cooperative Oncology Group Performance Score (ECOG PS) performance status 0-2
- Normal organ and marrow function as outlined in the protocol
- Left ventricular ejection fraction >/= 50%, as determined by radionuclide ventriculography (RVG) or echocardiogram within 60 days prior to initiation of protocol therapy
- Prior carboplatin is allowed if it was not given in conjunction with bevacizumab
- Prior trastuzumab is allowed
- No prior bevacizumab since diagnosis of CNS metastases or within 6 months prior to diagnosis of CNS metastases
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
Exclusion Criteria:
- Patients who have had chemotherapy within 14 days prior to entering the study, or those who have not recovered adequately from adverse events due to agents administered earlier
- Patients may not receive any concurrent investigational agents while on study
- Patients may not receive any cancer-directed concurrent therapy , such as concurrent chemotherapy, radiotherapy, or hormonal therapy while on study. Concurrent treatment with bisphosphonates is allowed
- History of Grade 3 or 4 allergic reactions attributed to compounds of similar or identical biologic composition to bevacizumab, carboplatin, or trastuzumab
- Known contraindication to MRI with gadolinium contrast, such as cardiac pacemaker, shrapnel, or ocular foreign body
- Leptomeningeal carcinomatosis as the only site of CNS involvement
- More than 2 seizures over last 4 weeks prior to study entry
- Grade 1 or higher CNS hemorrhage on baseline brain MRI
- History of grade 2 or higher CNS hemorrhage within 12 months of study entry
- Inadequately controlled hypertension
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infraction or unstable angina within 6 months prior to day 1
- Significant vascular disease within 6 months prior to day 1
- History of hemoptysis within 1 month prior to day 1
- Evidence of bleeding diathesis or significant coagulopathy
- Current, ongoing treatment with full-dose warfarin or its equivalent
- Use of aspirin (>325 mg/day) within 10 days prior to day 1
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 or anticipation of need for major surgical procedure during the course of the study.
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to day 1
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to day 1
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Proteinuria as demonstrated by a urine protein-creatinine ratio >/= 1.0 at screening
- Known hypersensitivity to any component of bevacizumab
- Pregnancy or lactation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: carboplatin, bevacizumab, trastuzumab (if HER2+)
Participants received treatment until disease progression in either CNS or non-CNS site. Cycle duration is 28 days. carboplatin: AUC=5 dose given intravenously on day 8 of cycle one and Day 1 of each subsequent cycle bevacizumab: 15 mg/kg dose given intravenously on day 1 of each cycle trastuzumab*: 6 mg/kg dose given intravenously on day 8 of each cycle for patients with HER2-positive breast cancer only *8mg/kg loading dose in cycle 1 for some participants HER-2: human epidermal growth factor receptor 2 |
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Central Nervous System (CNS) Objective Response Rate
Time Frame: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.
|
CNS objective response rate is the percentage of participants that achieve CNS complete or partial response as follows: CNS complete response (CR) is achieved if all of the following are satisfied:
CNS partial response (PR) is achieved if all of the following are satisfied: ->/= 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline
|
Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-Free Survival
Time Frame: Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum PFS follow-up for this study cohort was 18.6 months.
|
Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression (PD), second cancer, or death, whichever occurs first. PD if any of the following occur: CNS Disease
Non-CNS Disease • RECIST 1.0 criteria: at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded on treatment or the appearance of >/=1 new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Symptomatic
|
Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum PFS follow-up for this study cohort was 18.6 months.
|
CNS Best Response
Time Frame: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.
|
CNS best response was defined based on standard criteria. Adding to CR and PR (defined in the primary outcome measure): CNS stable disease (SD) is achieving all the following:
CNS Progressive Disease (PD) was experiencing any of the following: ->/- 40% increase in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline
|
Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.
|
Site of First Progression
Time Frame: Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum progression follow-up for this study cohort was 18.6 months.
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Site of first progression is classified as follows: CNS Disease
Symptomatic
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Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum progression follow-up for this study cohort was 18.6 months.
|
Overall Survival
Time Frame: Maximum survival follow-up for the study cohort was 66 months.
|
Participants were assessed every 6 months post-treatment.
Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
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Maximum survival follow-up for the study cohort was 66 months.
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Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Breast Neoplasms
- Brain Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Carboplatin
- Trastuzumab
- Bevacizumab
Other Study ID Numbers
- 09-224
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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