Breast CancerPhase 2NCT00546156
Preoperative Dose-dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab in Operable Breast Cancer
A Phase 2 study testing Doxorubicin, Cyclophosphamide and Paclitaxel in people with Breast Cancer, run by Ian E. Krop, MD, PhD at 4 sites in United States.
Trial summary
Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with bevacizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Doxorubicin, Cyclophosphamide and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2007to Dec 2012
- 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
- Documented primary invasive breast cancer by histologic assessment
- Tumors must express estrogen (ER) and/or progesterone receptors (PR) by standard immunohistochemical methods. Tumors must be negative for HER2. There must be sufficient sample for further protocol-specified immunohistochemical analysis
- Patients must have high risk ER+ or PR+ breast cancer as defined by criteria listed in protocol
- 18 year of age or older
- Performance status of 0 or 1 by ECOG criteria
- Use of an effective means of contraception in subjects of childbearing potential
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- Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to starting therapy.
- Patients taking exogenous sex-steroid hormone treatments for any reason at the time of diagnosis must discontinue all hormonal treatments at least 2 weeks prior to enrollment
- Patients must have preoperative treatment within 60 days of initial diagnosis of breast cancer
- No other malignancy that requires on-going treatment
- Normal organ function as outlined in the protocol
Who cannot join
- Prior cytotoxic chemotherapy or radiation for the current breast cancer
- Patients with inflammatory breast cancer
- HER2 positive disease defined as HER2-amplified by FISH or IHC 3+. HER2 2+ must be negative by FISH
- Known metastatic (Stage IV) disease
- Other investigational agents within 4 weeks prior to the start of study treatment
- Life expectancy of less than 6 months
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- Peripheral neuropathy greater than or equal to grade 2
- Inadequately controlled hypertension
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- NYHA grade II or greater congestive heart failure
- History of prior myocardial infarction
- History of unstable angina within 12 months prior to study enrollment
- Any history of stroke or transient ischemic attack at any time
- Known CNS disease
- Significant vascular disease
- Symptomatic peripheral vascular disease
- Evidence of significant bleeding within 6 months of study; any serious non-healing wound, skin ulcers, or bone fracture; any abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the past 6 months; any major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during course of study.
- Known HIV positive
- Unwilling to undergo pretreatment biopsy and consent to acquisition of archival tissue
- Pregnant of lactating
- Known hypersensitivity to any component of bevacizumab
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Dana-Farber at Faulkner Hospital
Boston, Massachusetts, 02130
New Hampshire Oncology-Hematology PA
Hooksett, New Hampshire, 03106
About this study
Official title: A Phase II Study of Preoperative Dose-dense (dd) Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel (T) With Bevacizumab in ER+ and/or PR+, HER2-negative Operable Breast Cancer
Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with bevacizumab. Bevacizumab is an antibody which works differently from the way other chemotherapy drugs work. Bevacizumab slows or stops cell growth in cancerous tumors by decreasing the blood supply to the tumors by binding to a substance found on cancer cells called VEGF (vascular endothelial growth factor). Bevacizumab is approved by the FDA for the treatment of colorectal cancer and lung cancer. However, it is not approved for the treatment of breast cancer. Another goal of this research is to determine whether we can develop a way to identify tumors that will respond well to this study treatment.
Read the detailed description
- To prepare for the surgery that will occur at the end of the study treatment, a small "clip" will be placed into the tumor area so that the surgeon can locate the site of the tumor at the time of surgery. This is a standard procedure for breast cancer.
- During the clip placement, a needle will be inserted into the tumor to measure interstitial fluid pressure (IFP measurement). IFP is done for research purposes to help understand how the tumor responds to the study treatment.
- Study treatment will begin with one dose of bevacizumab alone, followed two weeks later by chemotherapy and bevacizumab in eight two-week cycles. The study treatment will be given intravenously in the clinic.
- After the first dose of bevacizumab and prior to starting chemotherapy, a needle biopsy of the breast tumor will be performed for research purposes. A second measurement of IFP will also be done at this time.
- During the treatment period, tests and procedures will be performed at specified intervals and include the following: research MRI, physical exams, blood tests, urine tests, EKG, and MUGA or ECHO.
- Surgery to remove the tumor will occur no less than four weeks after the last dose of Paclitaxel.
- Conditions
- Breast Cancer
- Being tested
- Doxorubicin, Cyclophosphamide, Paclitaxel, Bevacizumab
- Keywords
- ER positive, PR positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxorubicinDrug
Also called Adriamycin
Standard chemotherapy regimen
CyclophosphamideDrug
Also called Cytoxan
Standard chemotherapy regimen
PaclitaxelDrug
Also called Taxol
Standard chemotherapy regimen
BevacizumabDrug
Also called Avastin
One intravenous dose given followed 2 weeks later with standard chemotherapy drugs and bevacizumab given intravenously in 8 two-week cycles.
| Study group | Role | What they receive |
|---|---|---|
| HR+, HER2- | Active comparator | Patients with Hormone Receptor Positive, HER2 negative Breast Cancer. A single dose of Bevacizumab 10mg/kg, followed two weeks later by Adriamycin60 mg/m2 and Cyclophosphamide 600 mg/m2 with Bevacizumab 10mg/kg every 2 weeks x4, followed by Taxol 175 mg/m2 with Bevacizumab 10 mg/kg every 2 weeks x3, followed by Taxol 175 mg/m2 x1. Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Bevacizumab |
| Triple Negative Breast Cancer Cohort | Active comparator | Hormone receptor negative, HER2 negative Cohort. Receive same drug protocol as Arm A. Receives: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response Rate After Preoperative Therapy in This Patient Population.
Pathological Complete response is defined as complete disappearance of invasive tumor in the breast at the time of surgery
Measured: 3 Years
Secondary outcomes (1)
Decrease in Interstitial Fluid Pressure.
To determine if bevacizumab monotherapy results in a decrease in interstitial fluid pressure
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionOct 2011
- Study completionDec 2012
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.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ian E. Krop, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Massachusetts General Hospital, Brigham and Women's Hospital, New Hampshire Oncology-Hematology PA
- Responsible party
- Sponsor-investigator, Ian E. Krop, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Ian Krop, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00546156
- Sponsor's protocol ID
- 07-130
- Status last verified
- Apr 2021
- First submitted
- 17 Oct 2007
- Last updated
- 18 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Preoperative Dose-dense (dd) Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel (T) With Bevacizumab in ER+ and/or PR+, HER2-negative Operable Breast Cancer
- ClinicalTrials.gov ID
- NCT00546156
- Acronym / sponsor ID
- 07-130
- Conditions
- Breast Cancer
- Keywords
- ER positive, PR positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Ian E. Krop, MD, PhDUniversity, hospital or other
- Collaborators
- Genentech, Inc., Massachusetts General Hospital, Brigham and Women's Hospital, New Hampshire Oncology-Hematology PA
- Study start
- Oct 2007
- Primary completion
- Oct 2011 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 18 Oct 2007 (estimated)
- Results
- Posted 10 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dose dense chemotherapy, which is the term for Adriamycin and Cyclophosphamide (AC) followed by Taxol chemotherapy given every two weeks, is the standard chemotherapy for the treatment of ER+ or PR+ breast cancer. In this trial, the standard chemotherapy is being combined with bevacizumab. Bevacizumab is an antibody which works differently from the way other chemotherapy drugs work. Bevacizumab slows or stops cell growth in cancerous tumors by decreasing the blood supply to the tumors by binding to a substance found on cancer cells called VEGF (vascular endothelial growth factor). Bevacizumab is approved by the FDA for the treatment of colorectal cancer and lung cancer. However, it is not approved for the treatment of breast cancer. Another goal of this research is to determine whether we can develop a way to identify tumors that will respond well to this study treatment.
Detailed description
- To prepare for the surgery that will occur at the end of the study treatment, a small "clip" will be placed into the tumor area so that the surgeon can locate the site of the tumor at the time of surgery. This is a standard procedure for breast cancer.
- During the clip placement, a needle will be inserted into the tumor to measure interstitial fluid pressure (IFP measurement). IFP is done for research purposes to help understand how the tumor responds to the study treatment.
- Study treatment will begin with one dose of bevacizumab alone, followed two weeks later by chemotherapy and bevacizumab in eight two-week cycles. The study treatment will be given intravenously in the clinic.
- After the first dose of bevacizumab and prior to starting chemotherapy, a needle biopsy of the breast tumor will be performed for research purposes. A second measurement of IFP will also be done at this time.
- During the treatment period, tests and procedures will be performed at specified intervals and include the following: research MRI, physical exams, blood tests, urine tests, EKG, and MUGA or ECHO.
- Surgery to remove the tumor will occur no less than four weeks after the last dose of Paclitaxel.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HR+, HER2- | Active comparator | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Paclitaxel, Drug: BevacizumabPatients with Hormone Receptor Positive, HER2 negative Breast Cancer. A single dose of Bevacizumab 10mg/kg, followed two weeks later by Adriamycin60 mg/m2 and Cyclophosphamide 600 mg/m2 with Bevacizumab 10mg/kg every 2 weeks x4, followed by Taxol 175 mg/m2 with Bevacizumab 10 mg/kg every 2 weeks x3, followed by Taxol 175 mg/m2 x1. |
| Triple Negative Breast Cancer Cohort | Active comparator | Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Paclitaxel, Drug: BevacizumabHormone receptor negative, HER2 negative Cohort. Receive same drug protocol as Arm A. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Documented primary invasive breast cancer by histologic assessment
- Tumors must express estrogen (ER) and/or progesterone receptors (PR) by standard immunohistochemical methods. Tumors must be negative for HER2. There must be sufficient sample for further protocol-specified immunohistochemical analysis
- Patients must have high risk ER+ or PR+ breast cancer as defined by criteria listed in protocol
- 18 year of age or older
- Performance status of 0 or 1 by ECOG criteria
Key exclusion criteria (21 listed)
- Prior cytotoxic chemotherapy or radiation for the current breast cancer
- Patients with inflammatory breast cancer
- HER2 positive disease defined as HER2-amplified by FISH or IHC 3+. HER2 2+ must be negative by FISH
- Known metastatic (Stage IV) disease
- Other investigational agents within 4 weeks prior to the start of study treatment
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 |
|---|---|---|
| DoxorubicinAlso: AdriamycinStandard chemotherapy regimen | Drug | HR+, HER2-, Triple Negative Breast Cancer Cohort |
| CyclophosphamideAlso: CytoxanStandard chemotherapy regimen | Drug | HR+, HER2-, Triple Negative Breast Cancer Cohort |
| PaclitaxelAlso: TaxolStandard chemotherapy regimen | Drug | HR+, HER2-, Triple Negative Breast Cancer Cohort |
| BevacizumabAlso: AvastinOne intravenous dose given followed 2 weeks later with standard chemotherapy drugs and bevacizumab given intravenously in 8 two-week cycles. | Drug | HR+, HER2-, Triple Negative Breast Cancer Cohort |
Primary outcome
Pathologic Complete Response Rate After Preoperative Therapy in This Patient Population.
Time frame: 3 Years
Pathological Complete response is defined as complete disappearance of invasive tumor in the breast at the time of surgery
1 secondary outcome
Decrease in Interstitial Fluid Pressure.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2021.
- 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.
Ian Krop, MD, PhD principal investigator
Dana-Farber Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxorubicin, Cyclophosphamide and Paclitaxel in people with Breast Cancer, run by Ian E. Krop, MD, PhD at 4 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 11 inclusion and 21 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 18 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 10 May 2013). 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?
Pathologic Complete Response Rate After Preoperative Therapy in This Patient Population. (time frame: 3 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 18 May 2021.