Breast CancerPhase 2NCT00618657
Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
A Phase 2 study testing Carboplatin, paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab in people with Breast Cancer and HER2-negative Breast Cancer, run by University of California, Irvine at 1 site in United States.
Trial summary
This phase II is studying the side effects and how well carboplatin and paclitaxel albumin-stabilized nanoparticle formulation when together with bevacizumab or trastuzumab before surgery works in treating patients with stage I-III breast cancer. Read more about this study
- Who is it for?
- Ages 21 to 90 years, women only
- Conditions the study is for
- Breast Cancer, HER2-negative Breast Cancer, HER2-positive Breast Cancer
- What is being tested?
- Carboplatin, paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Jul 2021
- 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 21 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
- Patients must be women with a histologically confirmed diagnosis of breast cancer that is more than 1 cm and or lymph node positive
- Physical examination, and scans needed for tumor assessment must be performed within 90 days prior to registration
- Patients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligible
- Serum creatinine within normal limits within 90 days prior to registration
- Bilirubin within normal limits within 90 days prior to registration
- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 2 x the institutional upper limit of normal within 90 days prior to registration
- Absolute neutrophil count (ANC) of >= 1,500/microliters within 90 days prior to registration
- Platelet count of >= 100,000/microliters within 90 days prior to registration
- Patients must have a performance status of 0-2 by Zubrod criteria
- Pregnant or nursing women may not participate; women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; pregnancy test required for women of childbearing potential
- In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday four weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines; if day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
Trial locations and contacts
1 site in 1 country.
United States1 site
Chao Family Comprehensive Cancer Center
Orange, California, 92868
About this study
Official title: A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
This phase II is studying the side effects and how well carboplatin and paclitaxel albumin-stabilized nanoparticle formulation when together with bevacizumab or trastuzumab before surgery works in treating patients with stage I-III breast cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) and monoclonal antibody therapy together before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate 2 year progression-free survival in patients with breast cancer more than 1 cm and/or lymph node positive breast cancer treated with weekly Carboplatin/Nab-Paclitaxel (with trastuzumab in patients with HER2+ disease, and with bevacizumab in HER2-).
II. To measure clinical response rates in patients treated in the neoadjuvant setting.
III. To measure the microscopic pathological response rate of this regimen in patients treated in the neoadjuvant setting.
IV. To measure the toxicity and delivered dose intensity of this regimen. V. To assess the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.
VI. To measure the outcome of patients treated with doxorubicin and cyclophosphamide with patients not treated with doxorubicin and cyclophosphamide.
SECONDARY OBJECTIVES:
- Develop quantitative analysis methods to obtain pre-treatment tumor characteristic morphological, enhancement kinetic, and Choline metabolic parameters in breast cancer. Select an optimal set of features using the logistic regression analysis and the Artificial Neural Network (ANN) to predict pathologic complete remission (pCR) in HER-2 positive and negative arm.
II. Investigate whether the early response patterns, analyzed using the percent tumor size changes, or changes in other lesion characteristic parameters, can be used to predict pathologic complete remission (pCR) in HER-2 positive and negative arm.
III. Investigate whether combining the pre-treatment tumor characteristic parameters, and the early response pattern during the treatment course, can achieve a higher "area under the receiver operating characteristic (ROC) curve" (AUC) in prediction of pCR than those based on pre-treatment MRI characteristics or tumor response patterns alone.
OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 60 minutes once weekly for 12 weeks. Patients with HER2-positive disease receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and patients with HER2-negative disease receive bevacizumab IV over 30-90 minutes once every two weeks for 5 doses. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 21-40 days later, patients undergo surgery.
After completion of study treatment, patients are followed for 5 years.
- Conditions
- Breast Cancer, HER2-negative Breast Cancer, HER2-positive Breast Cancer, Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer
- Being tested
- Carboplatin, paclitaxel albumin-stabilized nanoparticle formulation, bevacizumab, trastuzumab, magnetic resonance imaging
- Keywords
- pre-operative, neo-adjuvant, triple negative, HER2 positive, hormone receptor positive, breast, Carboplatin, Nab-paclitaxel, Trastuzumab, Bevacizumab, Inflammatory
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Carboplatin Hexal, Carboplatino, CBDCA
Given IV
paclitaxel albumin-stabilized nanoparticle formulationDrug
Also called Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxel
Given IV
bevacizumabDrug
Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, recombinant humanized anti-VEGF monoclonal antibody
Given IV
trastuzumabDrug
Also called anti-c-erB-2, MOAB HER2, monoclonal antibody c-erb-2, monoclonal antibody HER2
Given IV
magnetic resonance imagingProcedure or surgery
Also called MRI, NMR imaging, NMRI, nuclear magnetic resonance imaging
Optional correlative studies
therapeutic conventional surgeryProcedure or surgery
Post-chemotherapy surgery for patients with a response or stable disease must take place no sooner than 21 days after last dose of Herceptin; and 40 days after last dose of bevacizumab to allow for normalization of blood counts
| Study group | Role | What they receive |
|---|---|---|
| Arm I (HER-2 positive) | Experimental | Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, carboplatin IV over 60 minutes, and trastuzumab IV over 90 minutes , then weekly over 30-60 minutes. Treatment repeats every week for 12 weeks in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery. Receives: Drug: Carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: trastuzumab; Procedure: magnetic resonance imaging; Procedure: therapeutic conventional surgery |
| Arm II (HER-2 negative) | Experimental | Patients receive paclitaxel albumin-stabilized nanoparticle formulation and carboplatin as in Arm I. Patients also receive bevacizumab IV over 90 or 60 or 30 minutes once every two weeks for 5 doses in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery. Receives: Drug: Carboplatin; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Drug: bevacizumab; Procedure: magnetic resonance imaging; Procedure: therapeutic conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Progression is defined as a new lesion or a greater than or equal to 25% increase in the product of the largest perpendicular diameters of any one lesion on clinical exam or by ultrasound (U/S) or MRI. Analyzed using the Kaplan-Meier method. Cox proportional-hazards analysis will be used to derive the hazard ratio and 95% confidence interval between the two treatment arms, adjusted for clinical and demographic variables.
Measured: 2 years
Secondary outcomes (3)
Clinical Complete Response in the Neoadjuvant Setting
Defined as normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange. The 95% confidence interval (CI) will be computed.
Measured: Up to 5 years
Number of Participants With no Evidence of Microscopic pCR in the Neoadjuvant Setting
Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed.
Measured: Up to 5 years
Number of Participants With Toxicity of the Combinations in HER2 Positive and HER2 Negative Breast Cancer Assessed Using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0
The frequency of toxicities will be recorded.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionJul 2021
- Study completionJul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, IrvineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Rita Sanghvi, Mehta, University of California, Irvine
- Investigators
- Rita Mehta, M.D., Principal investigator, Chao Family Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00618657
- Sponsor's protocol ID
- 20076084
- Other IDs
- UCI 07-61, NCI-2010-00155, R01CA127927
- Status last verified
- Feb 2024
- First submitted
- 7 Feb 2008
- Last updated
- 28 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
- ClinicalTrials.gov ID
- NCT00618657
- Acronym / sponsor ID
- 20076084
- Conditions
- Breast Cancer, HER2-negative Breast Cancer, HER2-positive Breast Cancer, Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer
- Keywords
- pre-operative, neo-adjuvant, triple negative, HER2 positive, hormone receptor positive, breast, Carboplatin, Nab-paclitaxel
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- University of California, IrvineUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- Feb 2008
- Primary completion
- Jul 2021 (actual)
- Study completion
- Jul 2021 (actual)
- First posted
- 20 Feb 2008 (estimated)
- Results
- Posted 4 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II is studying the side effects and how well carboplatin and paclitaxel albumin-stabilized nanoparticle formulation when together with bevacizumab or trastuzumab before surgery works in treating patients with stage I-III breast cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) and monoclonal antibody therapy together before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed description
PRIMARY OBJECTIVES:
- To estimate 2 year progression-free survival in patients with breast cancer more than 1 cm and/or lymph node positive breast cancer treated with weekly Carboplatin/Nab-Paclitaxel (with trastuzumab in patients with HER2+ disease, and with bevacizumab in HER2-).
II. To measure clinical response rates in patients treated in the neoadjuvant setting.
III. To measure the microscopic pathological response rate of this regimen in patients treated in the neoadjuvant setting.
IV. To measure the toxicity and delivered dose intensity of this regimen. V. To assess the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.
VI. To measure the outcome of patients treated with doxorubicin and cyclophosphamide with patients not treated with doxorubicin and cyclophosphamide.
SECONDARY OBJECTIVES:
- Develop quantitative analysis methods to obtain pre-treatment tumor characteristic morphological, enhancement kinetic, and Choline metabolic parameters in breast cancer. Select an optimal set of features using the logistic regression analysis and the Artificial Neural Network (ANN) to predict pathologic complete remission (pCR) in HER-2 positive and negative arm.
II. Investigate whether the early response patterns, analyzed using the percent tumor size changes, or changes in other lesion characteristic parameters, can be used to predict pathologic complete remission (pCR) in HER-2 positive and negative arm.
III. Investigate whether combining the pre-treatment tumor characteristic parameters, and the early response pattern during the treatment course, can achieve a higher "area under the receiver operating characteristic (ROC) curve" (AUC) in prediction of pCR than those based on pre-treatment MRI characteristics or tumor response patterns alone.
OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 60 minutes once weekly for 12 weeks. Patients with HER2-positive disease receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and patients with HER2-negative disease receive bevacizumab IV over 30-90 minutes once every two weeks for 5 doses. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 21-40 days later, patients undergo surgery.
After completion of study treatment, patients are followed for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (HER-2 positive) | Experimental | Drug: Carboplatin, Drug: paclitaxel albumin-stabilized nanoparticle formulation, Drug: trastuzumab, Procedure: magnetic resonance imaging, Procedure: therapeutic conventional surgeryPatients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, carboplatin IV over 60 minutes, and trastuzumab IV over 90 minutes , then weekly over 30-60 minutes. Treatment repeats every week for 12 weeks in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery. |
| Arm II (HER-2 negative) | Experimental | Drug: Carboplatin, Drug: paclitaxel albumin-stabilized nanoparticle formulation, Drug: bevacizumab, Procedure: magnetic resonance imaging, Procedure: therapeutic conventional surgeryPatients receive paclitaxel albumin-stabilized nanoparticle formulation and carboplatin as in Arm I. Patients also receive bevacizumab IV over 90 or 60 or 30 minutes once every two weeks for 5 doses in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery. |
Who may qualify
- Ages
- 21 to 90 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarboplatinAlso: Carboplatin Hexal, Carboplatino, CBDCAGiven IV | Drug | Arm I (HER-2 positive), Arm II (HER-2 negative) |
| paclitaxel albumin-stabilized nanoparticle formulationAlso: Albumin-Stabilized Nanoparticle Paclitaxel, nab paclitaxel, nab-paclitaxel, nanoparticle albumin-bound paclitaxelGiven IV | Drug | Arm I (HER-2 positive), Arm II (HER-2 negative) |
| bevacizumabAlso: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, recombinant humanized anti-VEGF monoclonal antibodyGiven IV | Drug | Arm II (HER-2 negative) |
| trastuzumabAlso: anti-c-erB-2, MOAB HER2, monoclonal antibody c-erb-2, monoclonal antibody HER2Given IV | Drug | Arm I (HER-2 positive) |
| magnetic resonance imagingAlso: MRI, NMR imaging, NMRI, nuclear magnetic resonance imagingOptional correlative studies | Procedure or surgery | Arm I (HER-2 positive), Arm II (HER-2 negative) |
| therapeutic conventional surgeryPost-chemotherapy surgery for patients with a response or stable disease must take place no sooner than 21 days after last dose of Herceptin; and 40 days after last dose of bevacizumab to allow for normalization of blood counts | Procedure or surgery | Arm I (HER-2 positive), Arm II (HER-2 negative) |
Primary outcome
Progression Free Survival
Time frame: 2 years
Progression is defined as a new lesion or a greater than or equal to 25% increase in the product of the largest perpendicular diameters of any one lesion on clinical exam or by ultrasound (U/S) or MRI. Analyzed using the Kaplan-Meier method. Cox proportional-hazards analysis will be used to derive the hazard ratio and 95% confidence interval between the two treatment arms, adjusted for clinical and demographic variables.
3 secondary outcomes
Clinical Complete Response in the Neoadjuvant Setting
Time frame: Up to 5 years
Number of Participants With no Evidence of Microscopic pCR in the Neoadjuvant Setting
Time frame: Up to 5 years
Number of Participants With Toxicity of the Combinations in HER2 Positive and HER2 Negative Breast Cancer Assessed Using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rita Mehta, M.D. principal investigator
Chao Family Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carboplatin, paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab in people with Breast Cancer and HER2-negative Breast Cancer, run by University of California, Irvine at 1 site 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?
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 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 Oct 2023). 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?
Progression Free Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2024.