Breast CancerPhase 2NCT00027885
Phase II Bevacizumab + Tax In Advanced Breast Cancer
A Phase 2 study testing bevacizumab, cyclophosphamide and docetaxel in people with Breast Cancer, run by Case Comprehensive Cancer Center at 5 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. 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?
- bevacizumab, cyclophosphamide and docetaxel
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 5 sitesUnited States
- Study dates
- Nov 2001to Aug 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the breast
- Stage IIIA or IIIB
- Stage IV if patient has clinical evidence of locally advanced breast cancer only
- Inoperable disease
- Prior carcinoma in situ of the breast or bilateral breast cancer is allowed
- No CNS metastases
- Hormone receptor status:
- Estrogen and progesterone receptor status known
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex:
- Female or male
Menopausal status:
- Not specified
Performance status:
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy:
- More than 6 months
Hematopoietic:
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin normal (no greater than 2 times upper limit of normal [ULN] in patients with an inherited disorder)
- AST/ALT no greater than 2.5 times ULN
- INR and PTT normal
Renal:
- Creatinine normal OR
- Creatinine clearance at least 60 mL/min
- No proteinuria or clinically significant renal impairment
Cardiovascular:
- LVEF at least 45% by echocardiogram or MUGA scan
- No New York Heart Association class III or IV heart disease
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No inadequately controlled hypertension
- No history of deep vein thrombosis or other thromboses
- No clinically significant peripheral artery disease
- No arterial thromboembolic event within the past 6 months including the following:
- Transient ischemic attack
- Cerebrovascular accident
- Myocardial infarction
Other:
- No other prior or concurrent malignancy within the past 10 years except inactive nonmelanoma skin cancer or carcinoma in situ of the cervix
- No other uncontrolled concurrent illness
- No ongoing or active infection
- No non-healing wounds
- No psychiatric illness or social situation that would preclude study participation
- No prior allergic reaction to compounds of similar chemical or biological composition to bevacizumab, docetaxel, polysorbate 80 (Tween) formulations, or other agents used in this study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No concurrent cytokines during docetaxel/bevacizumab administration
- Concurrent cytokines during doxorubicin/cyclophosphamide administration allowed at the discretion of the treating physician
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Prior hormonal therapy (e.g., tamoxifen) allowed
Radiotherapy:
- Prior radiotherapy to affected breast allowed
Surgery:
- More than 28 days since prior major surgery
Other:
- At least 10 days since prior thrombolytic agents
- At least 10 days since prior full-dose oral or parenteral anticoagulants except to maintain patency of permanent indwelling IV catheters
- Concurrent warfarin allowed provided INR is less than 1.5
- Concurrent bisphosphonates allowed for osseous metastases provided they are not initiated on day 1 of cycle 1
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent full-dose oral or parenteral anticoagulants except to maintain patency of permanent indwelling IV catheters
- No concurrent thrombolytic agents
- No other concurrent anticancer agents or therapies
- No other concurrent investigational agents
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5055
UH-Southwest
Middleburg Heights, Ohio, 44130
UH-Chagrin Highlands
Orange, Ohio, 44122
UH-Green Road
South Euclid, Ohio, 44121
UH-Westlake
Westlake, Ohio, 44145
About this study
Official title: A Randomized Phase II Study of Bevacizumab in Combination With Docetaxel in Locally Advanced Breast Cancer
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.
PURPOSE: This randomized phase II trial is to see if docetaxel with or without bevacizumab followed by surgery, radiation therapy, and combination chemotherapy works better in treating patients who have stage III or stage IV breast cancer.
Read the detailed description
OBJECTIVES:
- Determine the effect of bevacizumab and docetaxel on reduction of microvessel density and induction of apoptosis of endothelial and tumor cells in patients with locally advanced breast cancer.
- Determine the safety profile of this regimen in these patients.
- Compare the effect of docetaxel and bevacizumab, in terms of objective response, stabilization of disease, and progression-free survival, in these patients.
OUTLINE: This is a randomized study. Patients are stratified according to disease stage. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.
- Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.
Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with estrogen and/or progesterone receptor-positive disease also receive oral tamoxifen daily for 5 years beginning after the completion of chemotherapy. Post-menopausal patients may receive oral anastrozole once daily for 5 years instead of tamoxifen.
Patients are followed at 3, 6, and 12 months, every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.
- Conditions
- Breast Cancer
- Being tested
- bevacizumab, cyclophosphamide, docetaxel, doxorubicin hydrochloride, adjuvant therapy
- Keywords
- stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
Patients receive bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.
cyclophosphamideDrug
Approximately 4 weeks after the completion of radiotherapy, patients receive cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
docetaxelDrug
Also called Taxotere
Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6.
Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
adjuvant therapyProcedure or surgery
After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.
Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
conventional surgeryProcedure or surgery
After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery.
neoadjuvant therapyProcedure or surgery
Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.
Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
radiation therapyRadiation
Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel | Active comparator | Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6. Receives: Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin hydrochloride; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy |
| Combine bevacizumab and docetaxel. | Experimental | Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8. Receives: Biological: bevacizumab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the ability of bevacizumab and docetaxel to reduce microvessel density and induce apoptosis of endothelial and tumor cells.
The primary outcome measure is the difference in change in biologic parameters between the two arms. Tumor biopsies are required to perform pre- and post-treatment tumor microvessel density determination, apoptosis by TUNEL assay, proliferation markers by immunohistochemistry(e.g. PCNA, Ki-67), and expression of nuclear clusterin/XIP8.
Measured: weeks 8 and 17
Secondary outcomes (1)
Number of patients with objective response
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startNov 2001
- Primary completionDec 2005
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Paula Silverman, MD, Study chair, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00027885
- Sponsor's protocol ID
- CWRU3100
- Other IDs
- U01CA062502, P30CA043703, CWRU-3100, NCI-2722
- Status last verified
- Jun 2013
- First submitted
- 7 Dec 2001
- Last updated
- 17 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Bevacizumab in Combination With Docetaxel in Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00027885
- Acronym / sponsor ID
- CWRU3100
- Conditions
- Breast Cancer
- Keywords
- stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2001
- Primary completion
- Dec 2005 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.
PURPOSE: This randomized phase II trial is to see if docetaxel with or without bevacizumab followed by surgery, radiation therapy, and combination chemotherapy works better in treating patients who have stage III or stage IV breast cancer.
Detailed description
OBJECTIVES:
- Determine the effect of bevacizumab and docetaxel on reduction of microvessel density and induction of apoptosis of endothelial and tumor cells in patients with locally advanced breast cancer.
- Determine the safety profile of this regimen in these patients.
- Compare the effect of docetaxel and bevacizumab, in terms of objective response, stabilization of disease, and progression-free survival, in these patients.
OUTLINE: This is a randomized study. Patients are stratified according to disease stage. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.
- Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.
Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with estrogen and/or progesterone receptor-positive disease also receive oral tamoxifen daily for 5 years beginning after the completion of chemotherapy. Post-menopausal patients may receive oral anastrozole once daily for 5 years instead of tamoxifen.
Patients are followed at 3, 6, and 12 months, every 6 months for 4 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Docetaxel | Active comparator | Drug: cyclophosphamide, Drug: docetaxel, Drug: doxorubicin hydrochloride, Procedure: adjuvant therapy, Procedure: conventional surgery, Procedure: neoadjuvant therapy, Radiation: radiation therapyPatients receive docetaxel IV over 1 hour once weekly on weeks 1-6. |
| Combine bevacizumab and docetaxel. | Experimental | Biological: bevacizumab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Procedure: adjuvant therapy, Procedure: conventional surgery, Procedure: neoadjuvant therapy, Radiation: radiation therapyPatients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- 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 |
|---|---|---|
| bevacizumabPatients receive bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8. | Biological | Combine bevacizumab and docetaxel. |
| cyclophosphamideApproximately 4 weeks after the completion of radiotherapy, patients receive cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. | Drug | Combine bevacizumab and docetaxel., Docetaxel |
| docetaxelAlso: TaxoterePatients receive docetaxel IV over 1 hour once weekly on weeks 1-6. | Drug | Docetaxel |
| doxorubicin hydrochlorideApproximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. | Drug | Combine bevacizumab and docetaxel., Docetaxel |
| adjuvant therapyAfter the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks. Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. | Procedure or surgery | Combine bevacizumab and docetaxel., Docetaxel |
| conventional surgeryAfter the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. | Procedure or surgery | Combine bevacizumab and docetaxel., Docetaxel |
| neoadjuvant therapyArm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8. Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. | Procedure or surgery | Combine bevacizumab and docetaxel., Docetaxel |
| radiation therapyThree to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks. | Radiation | Combine bevacizumab and docetaxel., Docetaxel |
Primary outcome
To evaluate the ability of bevacizumab and docetaxel to reduce microvessel density and induce apoptosis of endothelial and tumor cells.
Time frame: weeks 8 and 17
The primary outcome measure is the difference in change in biologic parameters between the two arms. Tumor biopsies are required to perform pre- and post-treatment tumor microvessel density determination, apoptosis by TUNEL assay, proliferation markers by immunohistochemistry(e.g. PCNA, Ki-67), and expression of nuclear clusterin/XIP8.
1 secondary outcome
Number of patients with objective response
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2013.
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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.
Paula Silverman, MD study chair
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
5 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 bevacizumab, cyclophosphamide and docetaxel in people with Breast Cancer, run by Case Comprehensive Cancer Center at 5 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?
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 17 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To evaluate the ability of bevacizumab and docetaxel to reduce microvessel density and induce apoptosis of endothelial and tumor cells. (time frame: weeks 8 and 17). 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 17 Jun 2013.