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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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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.
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention: Dtx Cyclophosphamide Bev | Experimental | Docetaxel 75m/m2 Cyclophosphamide 500 mg/m2 Bevacizumab 15 mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bevacizumab | Drug | IV 15mg/kg 21 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Participants were assessed during surgery, an average of one hour |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | At completion of chemotherapy treatment, an average of one hour |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Issam Makhoul, MD | University of Arkansas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32298288 | Derived | 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. | |
| 28045923 | Derived |
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This study recruited patients from September 9, 2005 through January 17, 2008. Patients were recruited from hematology/oncology clinic at the Winthrop P. Rockefeller Cancer Institute of the University of Arkansas for Medical Sciences.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | Docetaxel 75mg/m2 + Cyclophosphamide 500 mg/m2 + Avastin 15 mg/kg Q 3 weeks X 4 cycles Bevacizumab/Avastin: IV 15mg/kg 21 days Cyclophosphamide: 500mg per meter squared, IV every 21 days Doxorubicin: 60 mg per meter squared, IV every 21 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | Docetaxel 75mg/m2 + Cyclophosphamide 500 mg/m2 + Avastin 15 mg/kg Q 3 weeks X 4 cycles Bevacizumab/Avastin: IV 15mg/kg 21 days Cyclophosphamide: 500mg per meter squared, IV every 21 days Doxorubicin: 60 mg per meter squared, IV every 21 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | 90% Confidence Interval | percentage of evaluable patients | Participants were assessed during surgery, an average of one hour |
|
|
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If a subject experienced more than 1 of a given AE, the subject is only counted once for that AE. If a subject experienced more than one AE is a system organ class, the subject is only counted once in that system organ class.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | Docetaxel 75mg/m2 + Cyclophosphamide 500 mg/m2 + Avastin 15 mg/kg Q 3 weeks X 4 cycles Bevacizumab/Avastin: IV 15mg/kg 21 days Cyclophosphamide: 500mg per meter squared, IV every 21 days Doxorubicin: 60 mg per meter squared, IV every 21 days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| infection | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Issam Makhoul | University of Arkansas for Medical Sciences | 5016868274 | MakhoulIssam@uams.edu |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D003520 | Cyclophosphamide |
| D000077143 | Docetaxel |
| D004317 | Doxorubicin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Cyclophosphamide | Drug | 500mg per meter squared, IV every 21 days |
|
|
| Docetaxel | Drug | 60 mg per meter squared, IV every 21 days |
|
|
| Percentage of Participants With Grade 3 or 4 Adverse Events |
Percent of participants who had at least one grade 3 or 4 adverse event |
| 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 | 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 | at surgery, one day |
| Makhoul 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. |
| 24577164 | Derived | Makhoul 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. |
| 23563210 | Derived | Makhoul 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. |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Counts |
|---|
| Participants |
|
|
| Secondary | 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 | All participants evaluated surgically | Posted | Number | 90% Confidence Interval | percentage of pts w/ cCR | At completion of chemotherapy treatment, an average of one hour |
|
|
|
| Secondary | Percentage of Participants With Grade 3 or 4 Adverse Events | Percent of participants who had at least one grade 3 or 4 adverse event | Posted | Number | 90% Confidence Interval | percentage of pts w/ grade 3/4 AE | After each chemotherapy infusion, approximately one hour |
|
|
|
| Secondary | To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline | Absolute change in LVEF, where LVEF values are measured in percentage units | Posted | Mean | Standard Deviation | Percentage of LVEF | Immediately before treatment and 1 year after start of treatment |
|
|
|
| Secondary | Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer | pCR rate for triple negative patients--percent | Patients with triple negative breast cancer | Posted | Number | 90% Confidence Interval | % pCR among triple negative pts | at surgery, one day |
|
|
|
| 39 |
| 39 |
| 19 |
| 39 |
| pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea/vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Depression | Psychiatric disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Heart failure | Cardiac disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |