Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Vestibular Schwannoma

NCT01083966 | Suspended Phase 1

• 1 other identifier: 0912010765
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A recent study by Plotkin et al. showed that bevacizumab (Avastin) treatment was followed by clinically meaningful hearing improvement, tumor-volume reduction, or both in some, but not all, patients with Vestibular Schwannoma (VS) who were at risk for complete hearing loss or brain-stem compression from growing VS. Because of the promising results in preliminary studies of Bevacizumab and because of significant experience with the safety of the dosages proposed in this study, this study will offer a safe treatment for patients with VS. Therefore, this phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival and hearing function of patients with VS.

Conditions

Vestibular Schwannoma

Keywords

Vestibular; Schwannoma; earing-loss; brain-tumor; Acoustic; Neuroma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose.

  1 month post procedure

Secondary Outcomes (3)

• Composite overall response rate

  2 years

• Six-month progression-free survival (PFS)

  6 months

• Hearing response will be assessed in eligible patients

  6 months

Study Arms (1)

Avastin

EXPERIMENTAL

IA Avastin

Drug: Bevacizumab (Avastin)

Interventions

Bevacizumab (Avastin) DRUG

Super-Selective Intraarterial Intracranial Infusion of Bevacizumab in Vestibular Schwannoma This phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival and hearing function of patients with VS

Also known as: Avastin

Avastin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients of \>= 18 years of age.
• Patients with a documented diagnosis of unilateral or bilateral VS based on MRI and who have evidence of progressive vestibular schwannomas, and are considered poor candidates for surgery and radiation therapy or declined these treatments.
• Patients must have a Karnofsky performance status \>=60% (or the equivalent ECOG level of 0-2) (see Appendix A; Performance Status Evaluation) and an expected survival of \>= three months.
• No chemotherapy for two weeks prior to treatment under this research protocol and no external beam radiation for two weeks prior to treatment under this research protocol.
• Patients must have adequate hematologic reserve with WBC\>=3000/mm3, absolute neutrophils \>=1500/mm3 and platelets \>=100,000/ mm3. Patients who are on Coumadin must have a platelet count of \>=150,000/ mm3.
• Pre-enrollment chemistry parameters must show: bilirubin\< 1.5X the institutional upper limit of normal (IUNL); AST or ALT\< 2.5X IUNL and creatinine \< 1.5X IUNL.
• Pre-enrollment coagulation parameters (PT and PTT) must be \<1.5X the IUNL.
• Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.

You may not qualify if:

• Previous treatment with Avastin®.
• Women who are pregnant or lactating.
• Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.
• Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring including MRI with gadolinium.
• Surgery (including open biopsy), significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during study treatment.
• Current or recent (within 10 days of Avastin) use of aspirin (\> 325 mg/day), full dose (i.e., therapeutic dose) of oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes. Prophylactic use of anticoagulants is allowed (e.g., warfarin (1 mg qd) for catheter prophylaxis, and prophylactic low molecular-weight heparin (i.e., enoxaparin \[(40mg QD0\]).
• History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding.
• Inadequately controlled hypertension (blood pressure: systolic \> 150 mmHg and/or diastolic \> 100 mmHg).
• Patients with baseline urine dipstick for proteinuria \> 2+ must undergo a 24-hours urine collection and must demonstrate ≤ 1 g of protein in 24 hours.
• Clinically significant (i.e., active) cardiovascular disease (e.g., cerebrovascular accident or myocardial infarction within 6 months prior to randomization),unstable angina, congestive heart failure (NYHA Class ≥ II), or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with administration of study treatment.
• Serious non-healing sound, active peptic ulcer, or untreated bone fracture.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of enrollment.
• Known hypersensitivity to Avastin or any of its excipients.

Sponsors & Collaborators

• Northwell Health: lead
• Feinstein Institute for Medical Research: collaborator
• Hofstra North Shore: collaborator

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10075, United States

Location

MeSH Terms

Conditions

Neuroma, Acoustic; Neurilemmoma; Brain Neoplasms; Neuroma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Cranial Nerve Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Central Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• John Boockvar, MD

  Feinstein Institute for Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 10, 2010
• Study Start: August 1, 2011
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

US (1)