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A Pilot Study of Systemically Administered Bevacizumab in Patients With Neoplastic Meningitis (NM)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Neoplastic Meningitis

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Trial Information

A Pilot Study of Systemically Administered Bevacizumab in Patients With Neoplastic Meningitis (NM)


The Study Drug:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.

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 and 4:

- 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.

- 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.

At Weeks 6, 12, 18, and 24, and then every 8 weeks:

- 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.

- You will have a physical exam (Weeks .

- 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.

- Urine will be collected to test kidney function and for routine tests. If indicated
urine will be collected over a 24 hour period.

Every 2 weeks, your blood pressure will be measured.

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 25 patients will take part in this study. All will be enrolled at MD Anderson.


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 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 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 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Time Frame:

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 for 52 weeks

Safety Issue:

Yes

Principal Investigator

Ivo D. Tremont, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2009-0122

NCT ID:

NCT00924820

Start Date:

June 2009

Completion Date:

Related Keywords:

  • Neoplastic Meningitis
  • Neoplastic Meningitis
  • NM
  • Advanced Cancers
  • Brain Cancer
  • Advanced Cancer
  • Brain Diseases
  • Central Nervous System Disorders
  • CNS
  • Bevacizumab
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Spinal Cord
  • meninges
  • cerebrospinal fluid
  • CSF
  • Meningitis
  • Meningeal Carcinomatosis

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030