| City: |
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Houston |
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State:
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TX |
| Zip Code: |
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77030 |
| Conditions: |
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Neoplastic Meningitis |
| Purpose: |
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The goal of this clinical research study is to learn if and how Avastin (bevacizumab) may
affect cancer that has spread to the meninges of the brain or the spinal cord. The safety of
this drug will also be studied.
Primary Objectives:
1. Determine preliminary response data of intravenous bevacizumab in patients with NM:
1. As measured by clearance of malignant cells from the Cerebrospinal fluid (CSF) at
2, 4, 6, 12, 18, and 24 weeks, then every 8 weeks X 52 weeks, and
2. Time to neurological progression (TTNP)
Secondary Objectives:
1. Evaluate the safety of intravenous bevacizumab in patients with NM
2. Further describe the efficacy of this intervention as measured by a improvement of MR
imaging evidence of disease b. overall survival c. maintenance of quality of life
3. Determine effects of systemically administered bevacizumab on CSF, serum, and urine
Vascular endothelial growth factor (VEGF)levels levels
4. Correlate changes in CSF VEGF with response measurements.
5. Correlate primary tumor tissue VEGF expression with CSF VEGF levels
6. Correlate urine VEGF levels with serum and CSF VEGF levels
7. Evaluate serum and CSF VEGF index
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| Study summary: |
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The Study Drug:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.
Screening Visit:
You will have "screening tests" to help the study doctor decide if you are eligible to take
part in this study. This visit will be within 14 days before you receive the first dose of
study drug. If you have had some of these tests within the last 14 days, they may not need
to be repeated. The following tests and procedures will be performed:
- Your complete medical history will be recorded.
- You will have a physical exam, including measurement of your height, weight, and vital
signs (blood pressure, heart rate, breathing rate, and temperature).
- You will be asked how well you are able to perform the normal activities of daily
living (performance status).
- You will be asked about any drugs you may be taking.
- You will have a neurological exam. This is performed with a series of questions and
physical coordination tests, which should take about 20 minutes to complete. You will
be asked how well you are able to perform tasks that require you to use the part of
your brain in order to remember, communicate, and follow simple commands.
- Urine will be collected over a 24-hour period to test kidney function and for routine
tests.
- Samples of CSF from your spinal cord will be collected to look for the presence of
cancer cells. The spinal sample will be collected through a spinal tap. A spinal tap
(also called a lumbar puncture) is when fluid surrounding the spinal cord is removed by
inserting a needle into the lower back.
- Blood (about 3 1/2 tablespoons) will be drawn for routine tests and to check your
blood's ability to clot normally. This routine blood draw will include a pregnancy
test for women who are able to become pregnant. To take part in this study, the
pregnancy test must be negative.
- You will have a magnetic resonance imaging (MRI) scan to check the status of the
disease.
- Radioactive dye will be injected into the CSF to make sure the CSF flows freely
throughout the spinal canal. This is called an Indium-111 DPTA or Technetium 99m-DPTA
Flow Study. You will sign a separate consent form for this procedure, which will
describe the procedure and its risks in detail.
- You will be asked to complete a questionnaire about your quality of life. The
questionnaire will take about 5 minutes to complete.
- If you already have an Ommaya reservoir tap in place, samples of CSF from your brain
will be collected to look for the presence of cancer cells.
The study doctor will discuss the screening test results with you. If the screening tests
show that you are not eligible to take part in the study, you will not be enrolled. Other
treatment options will be discussed with you.
Study Drug Administration:
If you are found to be eligible to take part in this study, every 2 weeks, you will receive
bevacizumab by vein over about 1 hour.
Study Visits:
At Weeks 2, 4, 6, 12, 18, and 24, and then every 8 weeks, the following tests and procedures
will be performed:
- Samples of CSF from your spinal cord will be collected to check for the presence of
cancer cells.
- Blood (about 3 tablespoons) will be drawn for routine tests and to check your blood's
ability to clot normally.
- If you already have an Ommaya reservoir tap in place, samples of CSF from your brain
will be collected to look for the presence of cancer cells.
At Weeks 6, 12, 18, and 24, and then every 8 weeks, the following tests and procedures will
also be performed:
- You will have a physical exam.
- Your performance status will be recorded.
- You will be asked about any drugs you may be taking and if you have experienced any
side effects.
- You will have a neurological exam.
- You will complete the questionnaire about your quality of life.
- You will have an MRI scan to check the status of the disease.
Every 2 weeks, your blood pressure will be measured.
Every 6-8 weeks, urine will be collected over a 24-hour period to test kidney function and
for routine tests.
Length of Study:
You will be on study for up to 54 weeks (about 1 year). You will be taken off study early if
the disease gets worse or you experience intolerable side effects.
End-of-Study Visit:
If you go off study early, the following tests and procedures will be performed:
- You will have a physical exam.
- Your performance status will be recorded.
- You will have a neurological exam.
- Samples of CSF from your spinal cord will be collected to look for the presence of
cancer cells.
- Blood (about 3 tablespoons) will be drawn for routine tests and to check your blood's
ability to clot normally. You will complete the questionnaire about your quality of
life.
- If you already have an Ommaya reservoir tap in place, samples of CSF from your brain
will be collected to look for the presence of cancer cells.
Follow-up Visits:
If you do not go off study early, within 4 weeks after the last dose of study drug, every 4
weeks for 3 months, and then every 3 months from then on, you will have follow-up visits.
The following tests and procedures will be performed:
- You will have a physical exam.
- Your performance status will be recorded.
- You will have a neurological exam.
- Samples of CSF from your spinal will be collected to look for the presence of cancer
cells.
- Blood (about 3 tablespoons) will be drawn for routine tests and to check your blood's
ability to clot normally.
- You will have an MRI scan to check the status of the disease.
- If you already have an Ommaya reservoir tap in place, samples of CSF from your brain
will be collected to look for the presence of cancer cells.
This is an investigational study. Bevacizumab is FDA approved and commercially available
for the treatment of colon, breast, and lung cancer. Its use for the treatment of cancer
that has spread to the meninges of the brain or the spinal cord is investigational.
Up to 15 patients will take part in this study. All will be enrolled at M. D. Anderson. |
| Criteria: |
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Inclusion Criteria:
1. History of breast cancer, lung cancer or melanoma
2. Diagnosis of NM as proven either by: 1. positive CSF cytology, or 2. magnetic
resonance neuro-imaging, or 3. both
3. Age >/=18 years.
4. Routine laboratory studies adequate with bilirubin </= 1.5 x ULN, AST < 2.5 x ULN,
creatinine <1.0 x ULN, granulocytes >1500, platelets> 75,000; Hb >/= 9.0.
5. Patient able to sign informed consent and willing to participate in study primary
objectives
6. At least 1 week from last intrathecal chemotherapy (>2 weeks if liposomal
cytarabine). Patients are allowed to have received prior chemotherapy for their
tumor. No limit on prior chemotherapies will be made. Patients who have been treated
with tyrosine kinase inhibitors are permitted. Prior anti-VEGF targeted therapy is
not permitted, unless patient has been off anti-VEGF therapy for 6 months and did not
develop NM while on anti-VEGF therapy
7. KPS >/= 50%
8. Pre-treatment CSF Indium 111 CSF flow study without evidence of obstruction.
9. Patients on full-dose anticoagulants (e.g., warfarin) with PT INR >1.5 are eligible
provided that: 1. Patients are receiving anticoagulation (warfarin or low molecular
weight heparins (LMWH)) only if the patients can be off of warfarin for 4-5 days
prior to the LP and placed on LMWH in that interim, and if the 'treatment dose' of
LMWH can be safely held for 24 hours before and after the LP.
10. ( 9. continued) INR must be <1.2 prior to LP in this circumstance. If patients are
receiving thromboprophylaxis dose of LMWH, the patients can be enrolled, but the
thromboprophylaxis LMWH must be able to be safely held for 12 hours prior to the LP.
2. The patient has no active bleeding or pathological condition that carries a high
risk of bleeding 3. There is no evidence of serious or non-healing wound, ulcer or
bone fracture
11. Ventricular reservoir NOT mandatory
Exclusion Criteria:
1. Evidence of active CNS hemorrhage in the brain or tumor lesions
2. Besides NM, other known CNS disease, except for treated brain metastases(Patients
must be at least 1 month out from brain irradiation and have no evidence of
progression or hemorrhage at that time, as ascertained by clinical examination and
brain imaging (MRI or CT) during the screening period). Anticonvulsants (stable dose)
are allowed. Treatment for brain metastases may include whole brain radiotherapy,
radiosurgery or a combination as deemed appropriate by the treating physician.
3. (2. continued) With respect to irradiation for other purpose (for NM or bone
metastases, etc) patients need only 1 week out from the completion of irradiation.
Patients with CNS metastases treated by neurosurgical resection or brain biopsy
performed within 3 months prior to Day 1 will be excluded.
4. Patients with clinically significant cardiovascular disease are excluded 1)
Inadequately controlled HTN (SBP > 140 mmHg and/or DBP > 90 mmHg despite
antihypertensive medication). 2) Prior history of hypertensive crisis or hypertensive
encephalopathy. 3) New York Heart Association (NYHA) Grade II or greater congestive
heart failure.
5. ( 4. Continued) 4) History of myocardial infarction or unstable angina within 6
months prior to Day 1. 5) History of stroke or transient ischemic attack within 6
months prior to Day 1. 6) Significant vascular disease (e.g., aortic aneurysm,
requiring surgical repair or recent peripheral arterial thrombosis) within 6 months
prior to Day 1. 7) Clinically significant peripheral vascular disease. 8) Serious and
inadequately controlled cardiac arrhythmia
6. History of hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1
month prior to Day 1
7. Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation)
8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 or anticipation of need for major surgical procedure during the course
of the study
9. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to Day 1. Ventricular reservoir must have been
placed more than 28 days prior to Day 1.
10. History of abdominal fistula or gastrointestinal perforation within 6 months prior to
Day 1
11. Serious, non-healing wound, active ulcer, or untreated bone fracture
12. Proteinuria as demonstrated by UPC ratio >/=1.0 at screening or by urine dipstick >/=
2+. (Patients discovered to have >/= 2+ proteinuria on urinalysis at baseline should
undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours
to be eligible).
13. Known hypersensitivity to any component of bevacizumab
14. Intrathoracic or extrathoracic lung carcinoma of squamous cell histology. Mixed
tumors will be categorized by the predominant cell type unless small cell elements
are present, in which case the patient is ineligible; sputum cytology alone is
acceptable.
15. (14. continued) Patients with extrathoracic-only squamous cell NSCLC are eligible.
Patients with only peripheral lung lesions (of any non squamous NSCLC histology,
except small cell histology) will also be eligible (a peripheral lesion is defined as
a lesion in which the epicenter of the tumor is </= 2 cm from the costal or
diaphragmatic pleura in a three-dimensional orientation based on each lobe of the
lung and is >/= 2 cm from the trachea, main, and lobar bronchi).
16. Pregnant (positive pregnancy test) or nursing women. Angiogenesis is critical to
fetal development and the inhibition of angiogenesis following administration of
AVASTIN is likely to result in adverse effects on pregnancy. There are no adequate
and well-controlled studies in pregnant women. Both fertile men and women must agree
to use adequate contraceptive measures during study therapy and for at least 2 months
after the completion of bevacizumab therapy.
17. General Medical Exclusions 1) Inability to comply with study and/or follow-up
procedures 2) Life expectancy of less than 6 weeks 3) Current, recent (within 4 weeks
of the first infusion of this study), or planned participation in an experimental
drug study other than this Genentech supported study 4) Active malignancy, other than
superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of
the cervix within the last 5 years |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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February 17, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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