A Pilot Study of Bevacizumab for Neoplastic Meningitis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00924820
First received: June 18, 2009
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

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.

Objectives:

1. Primary:

1. Determine preliminary response data of intravenous bevacizumab in patients with NM

a. 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 up to 54 weeks, and

b. Time to neurological progression (TTNP)

2. Secondary:

  1. Evaluate the safety of intravenous bevacizumab in patients with NM
  2. Further describe the efficacy of this intervention as measured by

    1. improvement of MR imaging evidence of disease
    2. overall survival
    3. 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

Condition Intervention Phase
Neoplastic Meningitis
Drug: Bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Systemically Administered Bevacizumab in Patients With Neoplastic Meningitis (NM)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Response Rate [ 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 25
Study Start Date: June 2009
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab
Bevacizumab 10 mg/kg by vein over about 1 hour, every 2 weeks.
Drug: Bevacizumab
10 mg/kg by vein over about 1 hour, every 2 weeks.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00924820

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech
Investigators
Principal Investigator: Ivo D. Tremont, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00924820     History of Changes
Other Study ID Numbers: 2009-0122
Study First Received: June 18, 2009
Last Updated: November 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Meningitis
Meningeal Carcinomatosis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Antibodies
Antibodies, Monoclonal
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014