LymphedemaPhase 1NCT00318513
Safety Study of Bevacizumab to Treat Women With a History of Breast Cancer and Suffering From Upper Extremity Lymphedema
A Phase 1 study testing Bevacizumab in people with Lymphedema, run by Premiere Oncology of Arizona at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety and side effects of bevacizumab in subjects with lymphedema who will initially receive bevacizumab alone and then in combination with standard manual lymphatic drainage (MLD) and combined decongestive therapy (CDT). Read more about this study
- Who is it for?
- Ages 0 years and older, women only
- Conditions the study is for
- Lymphedema
- What is being tested?
- Bevacizumab
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Phase 1
- 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 0 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Women with a history of breast cancer status post (s/p) prior surgical resection (i.e., either lumpectomy and radiation, modified radical mastectomy or radical mastectomy) with lymphedema defined as a difference in limb volume of at least 500 ml by perometric assessment
- Lymphedema may be newly diagnosed or previously treated as long as it is Stage I (pitting) or II (fibrosis) at the time of study entry.
- No known evidence of recurrent or active metastatic breast cancer
- No prior chemotherapy within 6 months of study entry and has recovered to grade 1 or less from the toxicity of all prior chemotherapy or radiation therapy (with the exception of alopecia); ongoing anti-estrogen therapy for post-menopausal survivors is permissible.
- Normal end organ function defined as: serum creatinine < 1.5 mg/dl or a calculated creatinine clearance > 50 ml/min; SGOT and SGPT < 2.5 X upper limit of normal (ULN); total bilirubin < 1.5 X ULN; absolute neutrophil count (ANC) > 1,500 cells/µl; hemoglobin > 10 g/dl (without transfusions); platelet count > 100,000/µl; serum albumin within normal limits (WNL).
Who cannot join
- Stage III (lymphostatic elephantiasis) lymphedema
- Clinical evidence of bilateral lymphedema. Those patients who have undergone bilateral breast cancer surgery or prophylactic mastectomy on the non-cancerous breast will be excluded.
- Any prior history of deep venous thrombosis (DVT) or pulmonary embolus (with the exception of prior line-related thrombotic events) or myocardial infarction (MI), cerebrovascular accident (CVA) or any other arterial thromboembolic event (i.e., transient ischemic attack [TIA], reversible ischemic neurologic deficit [RIND], history of angina pectoris, clinically significant peripheral vascular disease with claudication, etc.)
- Patients with problems with wound healing (e.g., diabetic ulcers), gastrointestinal fistula
- Patients receiving therapeutic anti-coagulation including full dose aspirin or non-steroidal anti-inflammatory agents known to inhibit platelet function (low dose coumadin for port prophylaxis and low dose aspirin are allowed)
- Untreated hypertension with a baseline systolic blood pressure (SBP) of > 150 mmHg or a diastolic blood pressure (DBP) >100 mmHg will be excluded (stable treated hypertension with values less than those noted will be eligible).
Show all 14Show fewer
- A history of infectious complications of the involved arm or those with any contraindication to MLD + CB [e.g., congestive heart failure (CHF), DVT, acute or chronic renal failure] will be excluded.
- Women with a history of CHF [New York Heart Association (NYHA) Class II or greater] will be excluded.
- Pregnant or breast-feeding
- Unwilling to use an appropriate form of barrier contraception for the duration of the study and for three months following the last dose of bevacizumab
- Those patients who are actively undergoing MLD and/or CB at the time of study entry and for up to 4 weeks prior to entry
- Unable to provide written informed consent or to comply with study procedures
- Baseline urine protein : creatinine ratio > 1.0
- Known evidence of a bleeding diathesis or coagulopathy
Trial locations and contacts
1 site in 1 country.
United States1 site
Premiere Oncology of Arizona
Scottsdale, Arizona, 85260
Michael S Gordon, MD
About this study
Official title: Phase I Study Evaluating the Safety of Bevacizumab in Women With a History of Breast Cancer Suffering From Moderate to Severe Upper Extremity Lymphedema
The purpose of this study is to determine the safety and side effects of bevacizumab in subjects with lymphedema who will initially receive bevacizumab alone and then in combination with standard manual lymphatic drainage (MLD) and combined decongestive therapy (CDT). This study will help to determine the dose of bevacizumab to be used in future studies of subjects with lymphedema.
Read the detailed description
Lymphedema occurs with varying frequency in patients with cancer but approximately 10-15% of all breast cancer patients will develop lymphedema following breast cancer treatment. Lymphedema in breast cancer patients following axillary lymph node dissection is caused by the interruption of the axillary lymphatic system by surgery or radiation therapy, which causes an accumulation of fluid in the subcutaneous tissue of the arm, with decreased distensibility of tissue around the joints and increased weight of the extremity. The primary current therapy employed involves complete decongestive therapy (CDT) which encompasses the use of manual lymphatic drainage (MLD) and compression bandaging (CB) to the affected limb.
The specific contribution of the vascular system to the development of lymphedema is unclear. Vascular permeability is a complex process which is primarily controlled by the interaction of the ligand vascular endothelial growth factor (VEGF). As a result of the understanding of the biology of VEGF and the anecdotal appreciation of women with lymphedema who have noted improvement in their lymphedema while on VEGF inhibitor therapy, it is hypothesized that the reduction in vascular permeability resulting from the use of a VEGF inhibitor either alone or in conjunction with standard decongestive lymphedema therapy may significantly improve the outcome for patients with this post-operative complication.
Bevacizumab is a recombinant humanized monoclonal antibody directed against VEGF. Bevacizumab blocks the development of new blood vessels in cancer and it is approved by the FDA for the treatment of colon cancer in combination with chemotherapy. While bevacizumab has been administered to thousands of patients with cancer, there is only limited information about the use of bevacizumab in subjects without active cancer.
This study will evaluate the safety profile of escalating doses of bevacizumab administered intravenously alone for 4 weeks followed by 4 weeks of therapy in combination with manual lymph drainage (MLD) and compression bandaging (CB) to patients with moderate to severe unilateral upper extremity lymphedema due to prior breast cancer therapy.
- Conditions
- Lymphedema
- Being tested
- Bevacizumab
- Keywords
- breast cancer, lymphedema, extremity, women
- Medical subject headings
- Lymphedema, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2006 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for LymphedemaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants
Sponsor and investigators
- Lead sponsor
- Premiere Oncology of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Investigators
- Michael S Gordon, MD, Principal investigator, Premiere Oncology of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00318513
- Sponsor's protocol ID
- AVF3251s
- Status last verified
- Apr 2006
- First submitted
- 24 Apr 2006
- Last updated
- 10 May 2006
- Results posted
- No
Publications
Velanovich V, Szymanski W. Quality of life of breast cancer patients with lymphedema. Am J Surg. 1999 Mar;177(3):184-7; discussion 188. doi: 10.1016/s0002-9610(99)00008-2.
PubMed 10219851Yeoh EK, Denham JW, Davies SA, Spittle MF. Primary breast cancer. Complications of axillary management. Acta Radiol Oncol. 1986 Mar-Apr;25(2):105-8. doi: 10.3109/02841868609136386.
PubMed 3012953Brennan MJ, DePompolo RW, Garden FH. Focused review: postmastectomy lymphedema. Arch Phys Med Rehabil. 1996 Mar;77(3 Suppl):S74-80. doi: 10.1016/s0003-9993(96)90248-8.
PubMed 8599548Kobayashi MR, Miller TA. Lymphedema. Clin Plast Surg. 1987 Apr;14(2):303-13.
PubMed 3555946Mortimer PS. The pathophysiology of lymphedema. Cancer. 1998 Dec 15;83(12 Suppl American):2798-802. doi: 10.1002/(sici)1097-0142(19981215)83:12b+3.3.co;2-5.
PubMed 9874400Bates DO, Levick JR, Mortimer PS. Starling pressures in the human arm and their alteration in postmastectomy oedema. J Physiol. 1994 Jun 1;477(Pt 2):355-63. doi: 10.1113/jphysiol.1994.sp020197.
PubMed 7932226Svensson WE, Mortimer PS, Tohno E, Cosgrove DO. Increased arterial inflow demonstrated by Doppler ultrasound in arm swelling following breast cancer treatment. Eur J Cancer. 1994;30A(5):661-4. doi: 10.1016/0959-8049(94)90540-1.
PubMed 8080683Stanton AW, Holroyd B, Northfield JW, Levick JR, Mortimer PS. Forearm blood flow measured by venous occlusion plethysmography in healthy subjects and in women with postmastectomy oedema. Vasc Med. 1998;3(1):3-8. doi: 10.1177/1358836X9800300102.
PubMed 9666525Mellor RH, Stanton AW, Menadue L, Levick JR, Mortimer PS. Evidence for dermal angiogenesis in breast cancer related lymphedema demonstrated using dual-site fluorescence angiography. Microcirculation. 2002 Jul;9(3):207-19. doi: 10.1038/sj.mn.7800133.
PubMed 12080418Roberts CC, Stanton AW, Pullen J, Bull RH, Levick JR, Mortimer PS. Skin microvascular architecture and perfusion studied in human postmastectomy oedema by intravital video-capillaroscopy. Int J Microcirc Clin Exp. 1994 Nov-Dec;14(6):327-34. doi: 10.1159/000178851.
PubMed 7543461Mellor RH, Bush NL, Stanton AW, Bamber JC, Levick JR, Mortimer PS. Dual-frequency ultrasound examination of skin and subcutis thickness in breast cancer-related lymphedema. Breast J. 2004 Nov-Dec;10(6):496-503. doi: 10.1111/j.1075-122X.2004.21458.x.
PubMed 15569205Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med. 1992 Nov 1;176(5):1375-9. doi: 10.1084/jem.176.5.1375.
PubMed 1402682Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995 May;146(5):1029-39.
PubMed 7538264Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002 Nov 1;20(21):4368-80. doi: 10.1200/JCO.2002.10.088.
PubMed 12409337Yoshiji H, Kuriyama S, Hicklin DJ, Huber J, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Fukui H. The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model. Hepatology. 2001 Apr;33(4):841-7. doi: 10.1053/jhep.2001.23312.
PubMed 11283848
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Evaluating the Safety of Bevacizumab in Women With a History of Breast Cancer Suffering From Moderate to Severe Upper Extremity Lymphedema
- ClinicalTrials.gov ID
- NCT00318513
- Acronym / sponsor ID
- AVF3251s
- Conditions
- Lymphedema
- Keywords
- breast cancer, lymphedema, extremity, women
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants
- Lead sponsor
- Premiere Oncology of ArizonaUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- First posted
- 26 Apr 2006 (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.
The purpose of this study is to determine the safety and side effects of bevacizumab in subjects with lymphedema who will initially receive bevacizumab alone and then in combination with standard manual lymphatic drainage (MLD) and combined decongestive therapy (CDT). This study will help to determine the dose of bevacizumab to be used in future studies of subjects with lymphedema.
Detailed description
Lymphedema occurs with varying frequency in patients with cancer but approximately 10-15% of all breast cancer patients will develop lymphedema following breast cancer treatment. Lymphedema in breast cancer patients following axillary lymph node dissection is caused by the interruption of the axillary lymphatic system by surgery or radiation therapy, which causes an accumulation of fluid in the subcutaneous tissue of the arm, with decreased distensibility of tissue around the joints and increased weight of the extremity. The primary current therapy employed involves complete decongestive therapy (CDT) which encompasses the use of manual lymphatic drainage (MLD) and compression bandaging (CB) to the affected limb.
The specific contribution of the vascular system to the development of lymphedema is unclear. Vascular permeability is a complex process which is primarily controlled by the interaction of the ligand vascular endothelial growth factor (VEGF). As a result of the understanding of the biology of VEGF and the anecdotal appreciation of women with lymphedema who have noted improvement in their lymphedema while on VEGF inhibitor therapy, it is hypothesized that the reduction in vascular permeability resulting from the use of a VEGF inhibitor either alone or in conjunction with standard decongestive lymphedema therapy may significantly improve the outcome for patients with this post-operative complication.
Bevacizumab is a recombinant humanized monoclonal antibody directed against VEGF. Bevacizumab blocks the development of new blood vessels in cancer and it is approved by the FDA for the treatment of colon cancer in combination with chemotherapy. While bevacizumab has been administered to thousands of patients with cancer, there is only limited information about the use of bevacizumab in subjects without active cancer.
This study will evaluate the safety profile of escalating doses of bevacizumab administered intravenously alone for 4 weeks followed by 4 weeks of therapy in combination with manual lymph drainage (MLD) and compression bandaging (CB) to patients with moderate to severe unilateral upper extremity lymphedema due to prior breast cancer therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 0 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Women with a history of breast cancer status post (s/p) prior surgical resection (i.e., either lumpectomy and radiation, modified radical mastectomy or radical mastectomy) with lymphedema defined as a difference in limb volume of at least 500 ml by perometric assessment
- Lymphedema may be newly diagnosed or previously treated as long as it is Stage I (pitting) or II (fibrosis) at the time of study entry.
- No known evidence of recurrent or active metastatic breast cancer
- No prior chemotherapy within 6 months of study entry and has recovered to grade 1 or less from the toxicity of all prior chemotherapy or radiation therapy (with the exception of alopecia); ongoing anti-estrogen therapy for post-menopausal survivors is permissible.
- Normal end organ function defined as: serum creatinine < 1.5 mg/dl or a calculated creatinine clearance > 50 ml/min; SGOT and SGPT < 2.5 X upper limit of normal (ULN); total bilirubin < 1.5 X ULN; absolute neutrophil count (ANC) > 1,500 cells/µl; hemoglobin > 10 g/dl (without transfusions); platelet count > 100,000/µl; serum albumin within normal limits (WNL).
Key exclusion criteria (14 listed)
- Stage III (lymphostatic elephantiasis) lymphedema
- Clinical evidence of bilateral lymphedema. Those patients who have undergone bilateral breast cancer surgery or prophylactic mastectomy on the non-cancerous breast will be excluded.
- Any prior history of deep venous thrombosis (DVT) or pulmonary embolus (with the exception of prior line-related thrombotic events) or myocardial infarction (MI), cerebrovascular accident (CVA) or any other arterial thromboembolic event (i.e., transient ischemic attack [TIA], reversible ischemic neurologic deficit [RIND], history of angina pectoris, clinically significant peripheral vascular disease with claudication, etc.)
- Patients with problems with wound healing (e.g., diabetic ulcers), gastrointestinal fistula
- Patients receiving therapeutic anti-coagulation including full dose aspirin or non-steroidal anti-inflammatory agents known to inhibit platelet function (low dose coumadin for port prophylaxis and low dose aspirin are allowed)
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 |
|---|---|---|
| Bevacizumab | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2006.
- Background: PubMed 10219851Velanovich V, Szymanski W. Quality of life of breast cancer patients with lymphedema. Am J Surg. 1999 Mar;177(3):184-7; discussion 188. doi: 10.1016/s0002-9610(99)00008-2.
- Background: PubMed 3012953Yeoh EK, Denham JW, Davies SA, Spittle MF. Primary breast cancer. Complications of axillary management. Acta Radiol Oncol. 1986 Mar-Apr;25(2):105-8. doi: 10.3109/02841868609136386.
- Background: PubMed 8599548Brennan MJ, DePompolo RW, Garden FH. Focused review: postmastectomy lymphedema. Arch Phys Med Rehabil. 1996 Mar;77(3 Suppl):S74-80. doi: 10.1016/s0003-9993(96)90248-8.
- Background: PubMed 3555946Kobayashi MR, Miller TA. Lymphedema. Clin Plast Surg. 1987 Apr;14(2):303-13.
- Background: PubMed 9874400Mortimer PS. The pathophysiology of lymphedema. Cancer. 1998 Dec 15;83(12 Suppl American):2798-802. doi: 10.1002/(sici)1097-0142(19981215)83:12b+3.3.co;2-5.
- Background: PubMed 7932226Bates DO, Levick JR, Mortimer PS. Starling pressures in the human arm and their alteration in postmastectomy oedema. J Physiol. 1994 Jun 1;477(Pt 2):355-63. doi: 10.1113/jphysiol.1994.sp020197.
- Background: PubMed 8080683Svensson WE, Mortimer PS, Tohno E, Cosgrove DO. Increased arterial inflow demonstrated by Doppler ultrasound in arm swelling following breast cancer treatment. Eur J Cancer. 1994;30A(5):661-4. doi: 10.1016/0959-8049(94)90540-1.
- Background: PubMed 9666525Stanton AW, Holroyd B, Northfield JW, Levick JR, Mortimer PS. Forearm blood flow measured by venous occlusion plethysmography in healthy subjects and in women with postmastectomy oedema. Vasc Med. 1998;3(1):3-8. doi: 10.1177/1358836X9800300102.
- Background: PubMed 12080418Mellor RH, Stanton AW, Menadue L, Levick JR, Mortimer PS. Evidence for dermal angiogenesis in breast cancer related lymphedema demonstrated using dual-site fluorescence angiography. Microcirculation. 2002 Jul;9(3):207-19. doi: 10.1038/sj.mn.7800133.
- Background: PubMed 7543461Roberts CC, Stanton AW, Pullen J, Bull RH, Levick JR, Mortimer PS. Skin microvascular architecture and perfusion studied in human postmastectomy oedema by intravital video-capillaroscopy. Int J Microcirc Clin Exp. 1994 Nov-Dec;14(6):327-34. doi: 10.1159/000178851.
- Background: PubMed 15569205Mellor RH, Bush NL, Stanton AW, Bamber JC, Levick JR, Mortimer PS. Dual-frequency ultrasound examination of skin and subcutis thickness in breast cancer-related lymphedema. Breast J. 2004 Nov-Dec;10(6):496-503. doi: 10.1111/j.1075-122X.2004.21458.x.
- Background: PubMed 1402682Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med. 1992 Nov 1;176(5):1375-9. doi: 10.1084/jem.176.5.1375.
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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.
Michael S Gordon, MD principal investigator
Premiere Oncology of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bevacizumab in people with Lymphedema, run by Premiere Oncology of Arizona 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 5 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 10 May 2006. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael S Gordon, MD (480-860-5000, mgordon@premiereoncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00318513, which also lists 45 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 10 May 2006.