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Sponsors and Collaborators: |
Duke University Genentech |
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Information provided by: | Duke University |
ClinicalTrials.gov Identifier: | NCT00476827 |
Our hypothesis is that this study design, in which bevacizumab is added to one of six single agent chemotherapies with proven activity in metastatic breast cancer, will result in regression or stabilization of this disease in a safe and tolerable manner.
Condition | Intervention | Phase |
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Breast Cancer |
Drug: Bevacizumab (Avastin) Drug: Bevacizumab (avastin) |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Phase II Safety and Tolerability Study of Avastin When Added to Single-Agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain |
Estimated Enrollment: | 59 |
Study Start Date: | May 2007 |
Estimated Study Completion Date: | May 2020 |
Estimated Primary Completion Date: | May 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Active Comparator
Bevacizumab 15 mg/kg every 3 weeks in combination with Capecitabine (Xeloda), 2 weeks on and 1 week off on a every 3 week cycle.
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Drug: Bevacizumab (Avastin)
Bevacizumab(Avastin) 15 mg/kg every 3 weeks in combination with Capecitabine (Xeloda), 2 weeks on and 1 week off on a every 3 week cycle.
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2: Active Comparator
Docetaxel 35mg/m² IV over 60 min days 1, 8, and 15 in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
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Drug: Bevacizumab (Avastin)
Docetaxel 35mg/m² IV over 60 min days 1, 8, and 15 in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
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3: Active Comparator
CPT-11 (Irinotecan, Camptosar) - Patients being treated with an enzyme inducing antiepileptic drug (EIAED) will receive 340 mg/m² IV; others will receive 125 mg/m² IV 90 min on days 1 and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
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Drug: Bevacizumab (avastin)
CPT-11 (Irinotecan, Camptosar) - Patients being treated with an enzyme inducing antiepileptic drug (EIAED) will receive 340 mg/m² IV; others will receive 125 mg/m² IV 90 min on days 1 and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
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4: Active Comparator
Paclitaxel (Taxol)90 mg/m2 IV over 60-90 min days 1, 8, and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
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Drug: Bevacizumab (avastin)
Paclitaxel (Taxol)90 mg/m2 IV over 60-90 min days 1, 8, and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.
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5: Active Comparator
Vinorelbine Tartrate (Navelbine®) 25 mg/m² IV over 10 min days 1, 8 and 15 in combination with avastin 10 mg/kg IV on days 1 and 15 of a 28-day cycle.
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Drug: Bevacizumab (avastin)
Vinorelbine Tartrate (Navelbine®) 25 mg/m² IV over 10 min days 1, 8 and 15 in combination with avastin 10 mg/kg IV on days 1 and 15 of a 28-day cycle.
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6: Active Comparator
Gemcitabine (difluorodeoxycytidine, dFdC) 1000 mg/m2 IV on days 1 and 8 in combination with avastin 15 mg/kg IV on day 1 of a 21-day treatment cycle.
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Drug: Bevacizumab (avastin)
Gemcitabine (difluorodeoxycytidine, dFdC) 1000 mg/m2 IV on days 1 and 8 in combination with avastin 15 mg/kg IV on day 1 of a 21-day treatment cycle.
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There is an unmet clinical need for effective therapy of breast cancer that has metastasized to the brain. In this scenario, median survival is around 12 months using currently available therapeutic interventions. The majority of chemotherapy-based clinical trials have considered the presence of central nervous system metastasis an exclusion criterion due to the risk of toxicities, the inability of chemotherapeutic agents to cross the blood brain barrier, and the limited overall survival within this patient population.
The preclinical data regarding the safety and activity of bevacizumab in VEGF-expressing tumors provide a good rationale for its study in patients with breast cancer with metastasis to the brain. Yano, et al. illustrated that tumor cell expression of VEGF mRNA and protein directly correlated with angiogenesis and growth of brain metastasis in a nude mouse model. Transfecting the experimental cell lines known to produce visceral metastasis with an anti-sense VEGF-gene significantly reduced the incidence of brain metastasis. Kim, et al. illustrated that a murine model specific for brain metastases originating from breast cancer showed elevated expression of the angiogenic and permeability-inducing factor VEGF-A. The growth of the brain metastases in this model was attenuated by the addition of a VEGF-tyrosine kinase inhibitor via induction of apoptosis and decreased angiogenesis. VEGF has also been implicated in the development of brain edema, a significant source of the morbidity and mortality associated with brain metastasis. Enhanced levels of VEGF and its receptors have been reported in a murine model after induction of cortical ischemia. Finally, antagonism of VEGF was demonstrated to reduce both immediate and delayed volume of infarct.
The optimal dose of bevacizumab has been extensively studied in phase I trials alone and in combination with chemotherapy. The safe and effective dose has been established as 10 mg/kg q 14 days or 15 mg/kg Q 21 days. In addition to irinotecan and paclitaxel, it has been previously used in phase II/III settings in combination with capecitabine, vinorelbine, gemcitabine, and docetaxel. Phase III studies showed an overall survival advantage when bevacizumab was added to an irinotecan/5FU-based regimen for metastatic colorectal cancer, and when added to weekly paclitaxel for metastatic breast cancer.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Kathryn Clarke, BSN, MDA | 919-668-3810 | kathryn.clarke@duke.edu |
United States, Florida | |
Palm Beach Cancer Center Institute | Recruiting |
West Palm Beach, Florida, United States, 33401-3406 | |
Contact: Karen Minder, MD 561-366-4128 karen.minder@pbcancer.com | |
Principal Investigator: Elisabeth McKeen, MD | |
United States, North Carolina | |
Duke University Medical Center | Recruiting |
Durham, North Carolina, United States, 27710 | |
Contact: Renee Welch, RN 919-660-1278 renee.welch@duke.edu | |
Principal Investigator: Kimberly Blackwell, MD | |
Sub-Investigator: Kelly Marcom, MD | |
Sub-Investigator: Carey Anders, MD | |
Moses Cone Regional Cancer Center | Recruiting |
Greensboro, North Carolina, United States, 27403 | |
Contact: Vivian Sheidler, RN 336-832-0836 vivian.sheidler@mosescone.com | |
Principal Investigator: Peter Rubin, MD | |
Forsyth Regional Cancer Center | Recruiting |
Winston-Salem, North Carolina, United States, 27103-3079 | |
Contact: Elizabeth White 336-718-8461 ecwhite@novanthealth.com | |
Contact: Julie M Jester, BSHA 1-336-718-8491 jmjester@novanthealth.com | |
Principal Investigator: Judith Hopkins, MD | |
Presbyterian Health Care | Recruiting |
Charlotte, North Carolina, United States, 28204 | |
Contact: Jami Linn, BSN 704-384-8823 jalinn@novanthealth.com | |
Contact: Ruth King, RN 704-384-8920 | |
Principal Investigator: Richard Reiling, MD |
Principal Investigator: | Kimberly Blackwell, MD | Duke University |
Responsible Party: | Duke University Medical center ( Kimberly Blackwell, MD ) |
Study ID Numbers: | 9597-07-4R0, AVF4124s |
Study First Received: | May 18, 2007 |
Last Updated: | February 12, 2008 |
ClinicalTrials.gov Identifier: | NCT00476827 |
Health Authority: | United States: Food and Drug Administration; United States: Institutional Review Board |
Breast Cancer Metastatic Brain Anti-angiogenesis |
Docetaxel Capecitabine Vinorelbine Skin Diseases Paclitaxel Irinotecan |
Neoplasm Metastasis Breast Neoplasms Bevacizumab Gemcitabine Breast Diseases |
Neoplastic Processes Neoplasms Pathologic Processes Neoplasms by Site Antineoplastic Agents Therapeutic Uses |
Growth Substances Physiological Effects of Drugs Growth Inhibitors Angiogenesis Modulating Agents Angiogenesis Inhibitors Pharmacologic Actions |