Clinical trial NCT00492089: Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer
Official title: A Randomized Phase II Trial of Bevacizumab to Control Brain Radiation Damage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Anaplastic Meningioma
Adult Anaplastic Oligodendroglioma
Adult Brain Stem Glioma
Adult Central Nervous System Germ Cell Tumor
Adult Choroid Plexus Tumor
Adult Diffuse Astrocytoma
Adult Ependymoma
Adult Grade II Meningioma
Adult Grade III Meningioma
Adult Malignant Hemangiopericytoma
Adult Mixed Glioma
Adult Oligodendroglioma
Adult Papillary Meningioma
Adult Pineocytoma
Malignant Neoplasm
Meningeal Melanocytoma
Radiation Toxicity
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Adult Brain Tumor
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Lymphoepithelioma of the Oropharynx
Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Stage I Adenoid Cystic Carcinoma of the Oral Cavity
Stage I Basal Cell Carcinoma of the Lip
Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage I Lymphoepithelioma of the Nasopharynx
Stage I Lymphoepithelioma of the Oropharynx
Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage I Mucoepidermoid Carcinoma of the Oral Cavity
Stage I Salivary Gland Cancer
Stage I Squamous Cell Carcinoma of the Hypopharynx
Stage I Squamous Cell Carcinoma of the Larynx
Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage I Squamous Cell Carcinoma of the Nasopharynx
Stage I Squamous Cell Carcinoma of the Oropharynx
Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage I Verrucous Carcinoma of the Larynx
Stage I Verrucous Carcinoma of the Oral Cavity
Stage III Adenoid Cystic Carcinoma of the Oral Cavity
Stage III Basal Cell Carcinoma of the Lip
Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage III Mucoepidermoid Carcinoma of the Oral Cavity
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
Stage IV Basal Cell Carcinoma of the Lip
Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Lymphoepithelioma of the Oropharynx
Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
Stage IV Salivary Gland Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-06-27
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Bevacizumab may reduce CNS side effects caused by radiation therapy. This randomized phase II trial is studying how well bevacizumab works in reducing CNS side effects in patients who have undergone radiation therapy to the brain for primary brain tumor, meningioma, or head and neck cancer.

Detailed description: PRIMARY OBJECTIVE:

I. Determine to what extent bevacizumab can reduce active radiation toxicity to the CNS in patients who have undergone cranial irradiation for primary brain neoplasm, meningioma, or head and neck cancer.

SECONDARY OBJECTIVES:

I. Determine to what extent this drug can reduce dexamethasone dependence in these patients.

II. Determine to what extent this drug can improve neurologic function in these patients.

III. Determine to what extent this drug can improve quality of life of these patients.

OUTLINE: This is a randomized, placebo-controlled, crossover, double-blind study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients in arm II who have failed to respond to treatment at 6 or 12 weeks may cross over to arm I and receive 2 courses of bevacizumab as in arm I. Patients in arm I (including crossover patients) who have responded to treatment may receive 2 additional courses of bevacizumab.

Patients undergo MRI after courses 2 and 4.

Quality of life and neurologic function are assessed at baseline, periodically during study treatment, and at 12 and 24 weeks after completion of study treatment.

After completion of study treatment, patients are followed at 12 and 24 weeks.

Eligibility criteria: Inclusion Criteria:

* No evidence of bleeding diathesis or coagulopathy
* Fertile patients must use effective contraception during and for \>= 2 months after completion of study therapy
* No diarrhea \>= grade 1
* Histologically confirmed primary brain neoplasm, meningioma, or head and neck cancer \[WHO grade 2 or 3 disease--no WHO grade 4 primary brain neoplasms (i.e., glioblastoma or gliosarcoma)\]
* Patients with head and neck cancer must not have any of the following:

  * Evidence of metastatic disease
  * Evidence of tumor invasion to major vessels (e.g., the carotid)
  * History of bleeding related to tumor or radiotherapy during or after completion of radiotherapy
* Must have undergone cranial irradiation
* Must have radiographic evidence to support the diagnosis of radiation necrosis and/or surgical biopsy evidence of necrosis without tumor within the past 2 months
* Must have evidence of progressive neurologic signs or symptoms appropriate to the location of the radiation necrosis
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
* No significant traumatic injury within the past 28 days
* No evidence of active CNS hemorrhage
* Karnofsky performance status 60-100%
* No clinically significant cardiovascular disease, including any of the following:

  * Inadequately controlled hypertension (i.e., systolic BP \> 140 mm Hg and/or diastolic BP \> 90 mm Hg despite antihypertensive medication)
  * Large vessel cerebrovascular accident within the past 6 months
  * Myocardial infarction or unstable angina within the past 6 months
* No clinically significant cardiovascular disease, including any of the following:

  * NYHA class II-IV congestive heart failure
  * Serious or inadequately controlled cardiac arrhythmia
  * Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
  * Clinically significant peripheral vascular disease
* At least 6 months since prior radiotherapy
* Platelet count \> 75,000/mm\^3
* Granulocyte count \> 1,500/mm\^3
* Creatinine \< 1.0 times ULN
* AST \< 2.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Prior chemotherapy for tumor allowed
* Prior tyrosine kinase inhibitors of VEGF receptor (VEGFR) allowed
* More than 28 days since prior and no concurrent major surgical procedure or open biopsy
* Concurrent dexamethasone allowed provided patient is on a stable dose for \>= 1 week prior to study entry
* Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR \> 1.5 allowed provided the following criteria are met:

  * In-range INR (usually between 2 and 3) and patient is on a stable dose of oral anticoagulant for 1 week or on a stable dose of low molecular weight heparin
  * No active bleeding or pathological condition that carries a high risk of bleeding
* Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR \> 1.5 allowed provided the following criteria are met: No evidence of serious or nonhealing wound, ulcer, or bone fracture
* No concurrent chemotherapy or tyrosine kinase inhibitors of VEGFR
* No prior bevacizumab
* More than 7 days since prior core biopsy
* History of seizures allowed provided the patient is receiving anticonvulsant therapy
* Hemoglobin \>= 9.0 g/dL
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* No other concurrent investigational agents

Primary outcomes:
measure: Number of Participants With Response ( > 25% Reduction in T2 Flair) From Baseline to Evaluation at 6 Weeks Post Treatment
timeFrame: Baseline to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Monica Loghin
role: PRINCIPAL_INVESTIGATOR
References: