Breast CancerPhase 2NCT00203502
Primary Systemic Therapy in Operable/Locally Advanced Breast Cancer
A Phase 2 study testing Bevacizumab, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by University of Arkansas at 1 site in United States.
Trial summary
The main purpose of this study is to find out what effects taking the drug bevacizumab together with two chemotherapeutic agents, docetaxel and cyclophosphamide followed by doxorubicin alone before surgery will on breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Bevacizumab, Cyclophosphamide and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Feb 2015
- 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
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The diagnosis of breast cancer established by biopsy.
- Normal kidney function
- Normal LVEF evaluated by MUGA Scan
- >18 years of age
- Good performance status defined by ECOG scale of 0 or 1
- Consent
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- Women of childbearing potential must have a negative pregnancy test.
- Use of effective means of contraception in subjects of child-bearing potential while on treatment and for at least 3 months thereafter.
- Peripheral Neuropathy: must be < grade 1
- Hematologic (minimal values)
- Absolute neutrophil count >1,500/mm3
- Hemoglobin >8.0 g/dl
- Platelet count >100,000/mm3
- Hepatic
- Total bilirubin <ULN
- AST, ALT, Alkaline Phosphatase must be within range
Who cannot join
- Patients with locally advanced breast cancer with skin ulcerations
- Stage IV breast cancer
- Inflammatory breast cancer
- Allergy to any component of the treatment regimen
- Women who are breast feeding
- Pregnancy or refusal to use effective contraception
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- Inability to comply with study and/or follow-up procedures.
- Current, recent, or planned participation in a experimental drug study
- Blood pressure of >150/100 mmHg. Essential hypertension well controlled with anti hypertensives is not an exclusion criterion.
- unstable angina
- New York Heart Association Grade II or greater congestive heart failure
- history of myocardial infarction within 6 months
- history of stroke within 6 months
- Clinical significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Presence of central nervous system or brain metastasis
- major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0
- Minor surgical procedure such as fine needle aspirations or core biopsy within 7 days prior to day 0
- Pregnant or lactating
- Urine protein: creatinine ratio >1.0 at screening
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
- Serious, non-healing wound, ulcer, or bone fracture
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
Official title: Primary Systemic Therapy Using Sequential Docetaxel/Cyclophosphamide/Bevacizumab Followed by Doxorubicin in Operable/Locally Advanced Breast Cancer
The main purpose of this study is to find out what effects taking the drug bevacizumab together with two chemotherapeutic agents, docetaxel and cyclophosphamide followed by doxorubicin alone before surgery will on breast cancer. Bevacizumab will be given for twelve weeks in combination with chemotherapy then it ill be held during the administration of doxorubicin. Twenty-eight to fifty-six days after undergoing surgery, all patients will receive nine three-weekly infusions of bevacizumab.
Read the detailed description
Prior to being enrolled in this study, they will undergo an evaluation to determine eligibility. The study doctor will obtain a complete medical history, complete a physical examination including blood pressure and heart rate. The doctor will also obtain a baseline ECG as well as blood tests (approximately two tablespoons of blood). In order to decrease the effects of food, exercise and the sleep/wake cycle variability, all blood samples must be taken between 8AM - 10AM and patients will need to fast (no food or drink) for 10 hours prior to the blood test. Patients will also need to strain from working out prior to the blood test. The study will ask for a list of current medications. Patients will not be eligible if they have a history of or now require long-term anticoagulant (blood thinner) therapy (i.e. Coumadin or anything patients may be taking to prevent blood clots) have an allergy to bevacizumab or any other drugs used in the study.
Many of the following evaluations are commonly done to determine diagnosis and/or stage of breast cancer and may have already had some of all of them done. If the following procedures were not done within three weeks, they will need to be done again prior to receiving any study therapy.
- Diagnosis of breast cancer by fine needle aspiration or core needle biopsy will be required for entry in this study.
- Clip Placement - a clip will be placed in the tumor during the core biopsies as a marker to assist surgeons at the time of surgery.
- Tumor Clip Placements - a caliper is similar to a ruler and is used to measure the tumor from the outside of the body instead of always having to use an ultrasound or MRI.
- Tumor Ultrasound - this is a non-invasive exam that uses sound waves to produce a picture of your tumor.
All study participants will be treated with bevacizumab 15 mg/kg plus docetaxel 75 mg/m2 and cyclophosphamide 500 mg/m2 every three weeks for a total of four treatments. Three weeks after the completion of this part of the treatment patients will start receiving doxorubicin 60 mg/m2 every three weeks for a total of four treatments. All these drugs will be given as intravenous infusion on the first day of each three-week period.
Patients will come in for every three week visits and have a physical exam including blood pressure and heart rate. Medications lists will be taken and any side effects that may have been experienced. Tumor caliper measurements will be done and blood will be drawn at each of these visits.
A mammogram and MUGA scan will be done again just prior to surgery. Patients will undergo tumor surgery approximately six months after treatment. Patients will need to visit the study physician one month after surgery for another physical examination including blood pressure and heart rate, an assessment of any side effects and a list of current medications.
- Conditions
- Breast Cancer
- Being tested
- Bevacizumab, Cyclophosphamide, Docetaxel
- Keywords
- Operable and Locally advanced Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
IV 15mg/kg 21 days
CyclophosphamideDrug
Also called Cytoxan
500mg per meter squared, IV every 21 days
DocetaxelDrug
Also called Taxotere, Adriamycin
60 mg per meter squared, IV every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Intervention: Dtx Cyclophosphamide Bev | Experimental | Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg Receives: Drug: Bevacizumab; Drug: Cyclophosphamide; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Pathological Complete Response.
Pathological complete response was defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the resected breast.
Measured: Participants were assessed during surgery, an average of one hour
Secondary outcomes (4)
Number of Participants With Clinical Complete Response in Breast and the Axillary Lymph Nodes After the Completion of Chemotherapy and Bevacizumab.
Clinical complete response was defined using RECIST response categories as the clinical response to chemotherapy
Measured: At completion of chemotherapy treatment, an average of one hour
Percentage of Participants With Grade 3 or 4 Adverse Events
Percent of participants who had at least one grade 3 or 4 adverse event
Measured: After each chemotherapy infusion, approximately one hour
To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline
Absolute change in LVEF, where LVEF values are measured in percentage units
Measured: Immediately before treatment and 1 year after start of treatment
Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer
pCR rate for triple negative patients--percent
Measured: at surgery, one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionFeb 2015
- Study completionFeb 2015
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Issam Makhoul, MD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00203502
- Sponsor's protocol ID
- UARK 2004-59
- Status last verified
- May 2016
- First submitted
- 12 Sep 2005
- Last updated
- 11 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Hsu PC, Kadlubar SA, Siegel ER, Rogers LJ, Todorova VK, Su LJ, Makhoul I. Genome-wide DNA methylation signatures to predict pathologic complete response from combined neoadjuvant chemotherapy with bevacizumab in breast cancer. PLoS One. 2020 Apr 16;15(4):e0230248. doi: 10.1371/journal.pone.0230248. eCollection 2020.
PubMed 32298288Makhoul I, Todorova VK, Siegel ER, Erickson SW, Dhakal I, Raj VR, Lee JY, Orloff MS, Griffin RJ, Henry-Tillman RS, Klimberg S, Hutchins LF, Kadlubar SA. Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients. PLoS One. 2017 Jan 3;12(1):e0168550. doi: 10.1371/journal.pone.0168550. eCollection 2017.
PubMed 28045923Makhoul I, Griffin RJ, Siegel E, Lee J, Dhakal I, Raj V, Jamshidi-Parsian A, Klimberg S, Hutchins LF, Kadlubar S. High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer. Am J Clin Oncol. 2016 Jun;39(3):248-54. doi: 10.1097/COC.0000000000000046.
PubMed 24577164Makhoul I, Klimberg VS, Korourian S, Henry-Tillman RS, Siegel ER, Westbrook KC, Hutchins LF. Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer. Am J Clin Oncol. 2015 Feb;38(1):74-9. doi: 10.1097/COC.0b013e31828940c3.
PubMed 23563210
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Primary Systemic Therapy Using Sequential Docetaxel/Cyclophosphamide/Bevacizumab Followed by Doxorubicin in Operable/Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00203502
- Acronym / sponsor ID
- UARK 2004-59
- Conditions
- Breast Cancer
- Keywords
- Operable and Locally advanced Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Sep 2005
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Posted 5 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to find out what effects taking the drug bevacizumab together with two chemotherapeutic agents, docetaxel and cyclophosphamide followed by doxorubicin alone before surgery will on breast cancer. Bevacizumab will be given for twelve weeks in combination with chemotherapy then it ill be held during the administration of doxorubicin. Twenty-eight to fifty-six days after undergoing surgery, all patients will receive nine three-weekly infusions of bevacizumab.
Detailed description
Prior to being enrolled in this study, they will undergo an evaluation to determine eligibility. The study doctor will obtain a complete medical history, complete a physical examination including blood pressure and heart rate. The doctor will also obtain a baseline ECG as well as blood tests (approximately two tablespoons of blood). In order to decrease the effects of food, exercise and the sleep/wake cycle variability, all blood samples must be taken between 8AM - 10AM and patients will need to fast (no food or drink) for 10 hours prior to the blood test. Patients will also need to strain from working out prior to the blood test. The study will ask for a list of current medications. Patients will not be eligible if they have a history of or now require long-term anticoagulant (blood thinner) therapy (i.e. Coumadin or anything patients may be taking to prevent blood clots) have an allergy to bevacizumab or any other drugs used in the study.
Many of the following evaluations are commonly done to determine diagnosis and/or stage of breast cancer and may have already had some of all of them done. If the following procedures were not done within three weeks, they will need to be done again prior to receiving any study therapy.
- Diagnosis of breast cancer by fine needle aspiration or core needle biopsy will be required for entry in this study.
- Clip Placement - a clip will be placed in the tumor during the core biopsies as a marker to assist surgeons at the time of surgery.
- Tumor Clip Placements - a caliper is similar to a ruler and is used to measure the tumor from the outside of the body instead of always having to use an ultrasound or MRI.
- Tumor Ultrasound - this is a non-invasive exam that uses sound waves to produce a picture of your tumor.
All study participants will be treated with bevacizumab 15 mg/kg plus docetaxel 75 mg/m2 and cyclophosphamide 500 mg/m2 every three weeks for a total of four treatments. Three weeks after the completion of this part of the treatment patients will start receiving doxorubicin 60 mg/m2 every three weeks for a total of four treatments. All these drugs will be given as intravenous infusion on the first day of each three-week period.
Patients will come in for every three week visits and have a physical exam including blood pressure and heart rate. Medications lists will be taken and any side effects that may have been experienced. Tumor caliper measurements will be done and blood will be drawn at each of these visits.
A mammogram and MUGA scan will be done again just prior to surgery. Patients will undergo tumor surgery approximately six months after treatment. Patients will need to visit the study physician one month after surgery for another physical examination including blood pressure and heart rate, an assessment of any side effects and a list of current medications.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention: Dtx Cyclophosphamide Bev | Experimental | Drug: Bevacizumab, Drug: Cyclophosphamide, Drug: DocetaxelDocetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- The diagnosis of breast cancer established by biopsy.
- Normal kidney function
- Normal LVEF evaluated by MUGA Scan
- >18 years of age
- Good performance status defined by ECOG scale of 0 or 1
Key exclusion criteria (22 listed)
- Patients with locally advanced breast cancer with skin ulcerations
- Stage IV breast cancer
- Inflammatory breast cancer
- Allergy to any component of the treatment regimen
- Women who are breast feeding
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 |
|---|---|---|
| BevacizumabAlso: AvastinIV 15mg/kg 21 days | Drug | Intervention: Dtx Cyclophosphamide Bev |
| CyclophosphamideAlso: Cytoxan500mg per meter squared, IV every 21 days | Drug | Intervention: Dtx Cyclophosphamide Bev |
| DocetaxelAlso: Taxotere, Adriamycin60 mg per meter squared, IV every 21 days | Drug | Intervention: Dtx Cyclophosphamide Bev |
Primary outcome
Percentage of Participants With Pathological Complete Response.
Time frame: Participants were assessed during surgery, an average of one hour
Pathological complete response was defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the resected breast.
4 secondary outcomes
Number of Participants With Clinical Complete Response in Breast and the Axillary Lymph Nodes After the Completion of Chemotherapy and Bevacizumab.
Time frame: At completion of chemotherapy treatment, an average of one hour
Percentage of Participants With Grade 3 or 4 Adverse Events
Time frame: After each chemotherapy infusion, approximately one hour
To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline
Time frame: Immediately before treatment and 1 year after start of treatment
Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer
Time frame: at surgery, one day
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32298288Hsu PC, Kadlubar SA, Siegel ER, Rogers LJ, Todorova VK, Su LJ, Makhoul I. Genome-wide DNA methylation signatures to predict pathologic complete response from combined neoadjuvant chemotherapy with bevacizumab in breast cancer. PLoS One. 2020 Apr 16;15(4):e0230248. doi: 10.1371/journal.pone.0230248. eCollection 2020.
- Derived from this study: PubMed 28045923Makhoul I, Todorova VK, Siegel ER, Erickson SW, Dhakal I, Raj VR, Lee JY, Orloff MS, Griffin RJ, Henry-Tillman RS, Klimberg S, Hutchins LF, Kadlubar SA. Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients. PLoS One. 2017 Jan 3;12(1):e0168550. doi: 10.1371/journal.pone.0168550. eCollection 2017.
- Derived from this study: PubMed 24577164Makhoul I, Griffin RJ, Siegel E, Lee J, Dhakal I, Raj V, Jamshidi-Parsian A, Klimberg S, Hutchins LF, Kadlubar S. High-circulating Tie2 Is Associated With Pathologic Complete Response to Chemotherapy and Antiangiogenic Therapy in Breast Cancer. Am J Clin Oncol. 2016 Jun;39(3):248-54. doi: 10.1097/COC.0000000000000046.
- Derived from this study: PubMed 23563210Makhoul I, Klimberg VS, Korourian S, Henry-Tillman RS, Siegel ER, Westbrook KC, Hutchins LF. Combined neoadjuvant chemotherapy with bevacizumab improves pathologic complete response in patients with hormone receptor negative operable or locally advanced breast cancer. Am J Clin Oncol. 2015 Feb;38(1):74-9. doi: 10.1097/COC.0b013e31828940c3.
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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.
Issam Makhoul, MD principal investigator
University of Arkansas
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 Bevacizumab, Cyclophosphamide and Docetaxel in people with Breast Cancer, run by University of Arkansas 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?
The sponsor lists 16 inclusion and 22 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 11 May 2016. 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 5 Jan 2016). 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?
Percentage of Participants With Pathological Complete Response. (time frame: Participants were assessed during surgery, an average of one hour). 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 NCT00203502, which also lists 4 linked publications.
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 11 May 2016.