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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-03219 | Registry Identifier | Clinical Trial Reporting Program (CTRP) |
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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
| Case Comprehensive Cancer Center | OTHER |
| University of Pittsburgh | OTHER |
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The primary objectives are to determine the progression-free survival (PFS) and to evaluate safety of the trastuzumab, bevacizumab and docetaxel regimen.
Rationale: Antibodies are proteins that are normally part of the immune system that bind to foreign agents in the body. Researchers manufacture antibodies outside of the human body that bind to specific targets such as proteins in cancer cells. Herceptin is a monoclonal antibody that binds to the human epidermal growth factor receptor (HER-2), and can kill HER2-positive cancer cells. Herceptin is used to treat breast cancer that is HER2-positive, and has spread after treatment with other drugs. Bevacizumab is a signal transduction inhibitor that works by preventing the growth of new blood vessels from surrounding tissue into tumors. Bevacizumab specifically inhibits the vascular endothelial growth factor (VEGF), a substance made by cells that stimulates new blood vessel formation. Research indicates that HER-2 signaling helps to induce VEGF expression. Therefore, cancer treatments targeting both HER-2 and VEGF may improve anti-cancer efficacy in patients. Docetaxel is a chemotherapy agent used against breast and other types of cancer. The current study builds on previous research suggesting the safety and potential for efficacy with combination trastuzumab, bevacizumab, and docetaxel.
Purpose: The primary objectives are to determine the progression free survival and evaluate the safety of trastuzumab, bevacizumab, and docetaxel. Secondary objectives are to assess early changes in circulating tumor cells and circulating endothelial cells as predictors of progression free survival and clinical benefit, as well as to determine the overall clinical benefit rate.
Treatment: Study participants will be given trastuzumab, bevacizumab, and docetaxel. All study drugs will be given through intravenous infusions once every 21 days. A cycle is considered 3 weeks. A minimum of 6 study treatment cycles is required unless study participants experience disease growth or intolerable toxicity. The decision to stop docetaxel after 6 cycles is up to the discretion of the treating physician and the patient. Study participants who are deriving a benefit from the study drugs may continue on trastuzumab and bevacizumab alone. Several tests and exams will be given throughout the study to closely monitor study participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trastuzumab, Bevacizumab, and Docetaxel | Experimental | Trastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M²] |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trastuzumab | Drug | administered every three weeks on day 1, every 21 days. The dose given will be 6 mg/kg. The initial loading dose is 8mg/kg and is administered as a 90-minute infusion. Thereafter, the maintenance dose is 6mg/kg every three weeks administered as a 30 minute infusion (unless the treating physician indicates a longer infusion duration is warranted). Trastuzumab is given prior to bevacizumab. Trastuzumab is to be continued until disease progression or unacceptable toxicity. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen. | The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months. | up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in CTCs as Predictors of PFS and Clinical Benefit | Circulating tumor cells (CTCs) evaluated at baseline (day 1 of treatment) and after 1 treatment cycle (day 22 prior to cycle 2 treatment). | Day 1 and Day 22 |
| Overall Clinical Benefit Rate (CR+PR+SD) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bhuvaneswari Ramaswamy, MD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States | ||
| Ohio State University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18316792 | Result | Puhalla S, Mrozek E, Young D, Ottman S, McVey A, Kendra K, Merriman NJ, Knapp M, Patel T, Thompson ME, Maher JF, Moore TD, Shapiro CL. Randomized phase II adjuvant trial of dose-dense docetaxel before or after doxorubicin plus cyclophosphamide in axillary node-positive breast cancer. J Clin Oncol. 2008 Apr 1;26(10):1691-7. doi: 10.1200/JCO.2007.14.3941. Epub 2008 Mar 3. |
| Label | URL |
|---|---|
| Jamesline | View source |
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September 2007 and November 2012
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| ID | Title | Description |
|---|---|---|
| FG000 | Trastuzumab, Bevacizumab, and Docetaxel | Trastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M²] |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Trastuzumab, Bevacizumab, and Docetaxel | Trastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M²] |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen. | The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months. | Posted | Median | 95% Confidence Interval | months | up to 3 years |
|
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NCI Common Toxicity Criteria (CTC) version 3.0 was utilize the CTC for adverse event reporting.
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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 | Trastuzumab, Bevacizumab, and Docetaxel | Trastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M²] |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bhuvaneswari Ramaswamy, MD | The Ohio State University Comprehensive Cancer Center | 614-293-0066 | Bhuvaneswari.Ramaswamy@osumc.edu |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000068878 | Trastuzumab |
| D000068258 | Bevacizumab |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
|
| Bevacizumab | Drug | administered every three weeks on day 1, every 21 days. The dose given will be 15 mg/kg. The initial dose is administered over 90 minutes. If the first infusion is well tolerated, the second dose is given over 60 minutes, and if that is well tolerated, then subsequent doses may be given over 30 minutes. Avastin is given after trastuzumab and prior to docetaxel. |
|
|
| Docetaxel | Drug | administered every three weeks on day 1, every 21 days. The dose given will be 75 mg/M². All doses of docetaxel are administered over 60 minutes. Docetaxel is given after trastuzumab and bevacizumab. |
|
|
Defined as best response of CR or PR or stable disease for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions |
| at least 24 weeks |
| Changes in CECs as Predictors of PFS and Clinical Benefit | Circulating endothelial cells (CECs) are to be collected day 1 prior to treatment and day 22 prior to treatment. These samples are to be collected at the PI's discretion based upon the availability of the cell processing laboratory, the patients will be informed when consented if the samples will collected or not. | Day 1 and Day 22 |
| Columbus |
| Ohio |
| 43210 |
| United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | patients |
|
|
|
| Secondary | Changes in CTCs as Predictors of PFS and Clinical Benefit | Circulating tumor cells (CTCs) evaluated at baseline (day 1 of treatment) and after 1 treatment cycle (day 22 prior to cycle 2 treatment). | Due to sample size, could not perform any statistical analysis to correlate the baseline CTCs with PFS and response rate. Samples only available for 50% of the patients. | Posted | Number | patients with detected CTCs | Day 1 and Day 22 |
|
|
|
| Secondary | Overall Clinical Benefit Rate (CR+PR+SD) | Defined as best response of CR or PR or stable disease for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions | Posted | Number | 95% Confidence Interval | percent of patients | at least 24 weeks |
|
|
|
| Secondary | Changes in CECs as Predictors of PFS and Clinical Benefit | Circulating endothelial cells (CECs) are to be collected day 1 prior to treatment and day 22 prior to treatment. These samples are to be collected at the PI's discretion based upon the availability of the cell processing laboratory, the patients will be informed when consented if the samples will collected or not. | CEC data was not collected and available for analysis | Posted | Day 1 and Day 22 |
|
|
| 0 |
| 26 |
| 26 |
| 26 |
| Neutropenia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever without neutropenia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hand-foot syndrome | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| decreased LVEF | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headaches | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision changes | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Wound Complication | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Increased lacrimation | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |