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Metastatic Breast CancerPhase 2NCT01004172

Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

A Phase 2 study testing carboplatin, bevacizumab and herceptin in people with Metastatic Breast Cancer and Breast Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this research study is to determine how well the combination of bevacizumab and carboplatin works in treating breast cancer that has spread to the brain. Bevacizumab is an antibody (a protein that attacks a foreign substance in the body) that is made in the laboratory. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
carboplatin, bevacizumab and herceptin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
3 sitesUnited States
Study dates
Nov 2009to Feb 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase II Trial of Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases

The purpose of this research study is to determine how well the combination of bevacizumab and carboplatin works in treating breast cancer that has spread to the brain. Bevacizumab is an antibody (a protein that attacks a foreign substance in the body) that is made in the laboratory. Bevacizumab works differently from the way chemotherapy drugs work. Usually chemotherapy drugs attack fast growing cancer cells in the body. Bevacizumab works to slow or stop the growth of cells in cancer tumors by decreasing the blood supply to the tumors. When the blood supply is decreased, the tumors don't get the oxygen and nutrients they need to grow. Carboplatin is in a class of drugs known as platinum-containing compounds and has been approved for use in the treatment of ovarian cancer. Information from other research studies suggests that the combination of bevacizumab with carboplatin may be effective in treating breast cancer.

Read the detailed description

This study used a two-stage design to evaluate efficacy bevacizumab and carboplatin based on Central Nervous System (CNS) response. The null and alternative therapy response rates are 5% versus 20%. If 1 or more participants assessable in the stage one cohort (n=12 assessable participants) achieve CNS response then accrual proceeds to stage two (n=25 additional assessable participants). If at least 4 participants in the final set of 37 assessable participants achieve CNS response then this regimen would be deemed worthy of further study. The probability of stopping early is 0.54 if the true CNS response rate is 5% and 0.07 if the true CNS response rate is 20%. The probability of deeming the treatment worthy of further study is 0.10 and 0.90 if the true CNS response rate is 5% and 20%, respectively.

Being tested
carboplatin, bevacizumab, herceptin
Keywords
carboplatin, bevacizumab
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01004172
Study groupRoleWhat they receive
carboplatin, bevacizumab, trastuzumab (if HER2+)ExperimentalParticipants 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
Receives: Drug: carboplatin; Drug: bevacizumab; Drug: herceptin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Central Nervous System (CNS) Objective Response Rate

    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:

    • Complete resolution of all measurable (>= 1 cm in longest dimension [LD]) and non-measurable brain metastases
    • No new CNS lesions (defined as any new lesion >= 6 mm in LD)
    • Stable or decreasing steroid dose
    • No new/progressive tumor-related neurologic signs or symptoms
    • No progression of extra-CNS disease as assessed by RECIST

    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

    • No progression on non-measurable lesions
    • No new CNS lesions (defined as any new lesion >/= 6 mm in LD)
    • Stable or decreasing steroid dose
    • No new/progressive tumor-related neurologic signs or symptoms
    • No progression of extra-CNS disease as assessed by RECIST

    Measured: 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 outcomes (4)

  1. Progression-Free Survival

    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

    • >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment
    • Progression of non-measurable lesions
    • New lesions (>/=6 mm)

    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

    • Increasing steroid requirement
    • Global deterioration of health status requiring discontinuation of treatment
    • New/progression tumor-related neurologic signs and symptoms except for transient worsening lasting </=14 days

    Measured: 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.

  2. CNS Best Response

    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:

    • < 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline
    • No progression on non-measurable lesions
    • No new CNS lesions (defined as any new lesion >/= 6 mm in LD)
    • Stable or decreasing steroid dose
    • No new/progressive tumor-related neurologic signs or symptoms
    • No progression of extra-CNS disease as assessed by RECIST

    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

    • Progression on non-measurable lesions
    • New CNS lesions (defined as any new lesion >/= 6 mm in LD)
    • Increasing steroid dose
    • New/progressive tumor-related neurologic signs or symptoms
    • Progression of extra-CNS disease as assessed by RECIST

    Measured: 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.

  3. Site of First Progression

    Site of first progression is classified as follows:

    CNS Disease

    • >/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment
    • Progression of non-measurable lesions
    • New lesions (>/=6 mm) Non-CNS Disease
    • Per RECIST 1.0 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more 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

    • Increasing steroid requirement
    • Global deterioration of health status requiring discontinuation of treatment
    • New/progression tumor-related neurologic signs and symptoms (NSS) except for transient worsening lasting </=14 days

    Measured: 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.

  4. Overall Survival

    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.

    Measured: Maximum survival follow-up for the study cohort was 66 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionDec 2013
  4. Study completionFeb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01004172
Sponsor's protocol ID
09-224
Status last verified
Dec 2018
First submitted
28 Oct 2009
Last updated
14 Dec 2018
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Leone JP, Emblem KE, Weitz M, Gelman RS, Schneider BP, Freedman RA, Younger J, Pinho MC, Sorensen AG, Gerstner ER, Harris G, Krop IE, Morganstern D, Sohl J, Hu J, Kasparian E, Winer EP, Lin NU. Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases. Breast Cancer Res. 2020 Nov 30;22(1):131. doi: 10.1186/s13058-020-01372-w.

    PubMed 33256829

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing carboplatin, bevacizumab and herceptin in people with Metastatic Breast Cancer and Breast Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01004172, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2018.

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