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Temozolomide, Bevacizumab, Lithium and Radiation Treatment for Newly Diagnosed High Grade Glioma: A Phase II Study

Phase 2
18 Years
Open (Enrolling)
Brain Cancer

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Trial Information

Temozolomide, Bevacizumab, Lithium and Radiation Treatment for Newly Diagnosed High Grade Glioma: A Phase II Study

Cycle 1 (42-day cycle):

Temozolomide will be taken at a dose of 75 mg/m^2 orally, beginning the night prior to the
first radiation treatment. Duration of temozolomide treatment is 42 consecutive days.

Radiation therapy must begin within 3-5 weeks of surgery. Treatment of 1.8 Gy will be given
daily for 5 days per week, Monday through Friday. Treatment will continue for 33 fractions
for a total dose of 59.4 Gy over 6.5 weeks. All portals shall be treated during each
treatment session. Doses are specified as the target dose that shall be to the center of
the target volume.

Bevacizumab will be added to the temozolomide/radiation treatment plan 29(+3 if necessary)
days post surgery . This may be delayed to ensure that 28 days has elapsed between surgery
and the first dose of bevacizumab. No patient will be treated with bevacizumab before 28
days after a surgical procedure.

Bevacizumab treatment continues until the first post-treatment MRI is performed.
Radiological re-evaluation by MRI with gadolinium contrast with perfusion sequences will be
performed at 35 days (+ 2 days) after completion of radiation therapy. Assessment of
response will continue to be performed following every 2 cycles.

Treatment Cycle 2-7 (28 day cycles):

If the Cycle 1 post-treatment MRI is stable or without sign of recurrent tumor the
subsequent cycles (Cycles 2 - 7) will be administered as follows:

- Temozolomide at a dose of 150 mg/m^2 will be taken orally on Days 1-7

- Bevacizumab will be administered at a dose of 10 mg/kg per dosing administration on Day
8 and Day 22

- Magnetic Resonance Imaging is performed after every 2 cycles

Lithium Carbonate: Initiate treatment at 300 mg PO BID; increase dose every 7 days by 300 mg
to goal total dose of 1200 mg per day. Serum levels will than be assessed and dose adjusted
until therapeutic level of 0.8 to 1.2 mEq/L is reached. Adjust dose according to clinical
response and trough serum level (12 h) after steady state is reached (4-5 days).

Inclusion Criteria:

- Newly diagnosed high grade glioma (WHO Grade III and IV)

- Brain magnetic resonance imaging (MRI) scan with gadolinium contrast

- Patient must have normal organ and marrow function as defined below:

- Absolute neutrophil count >= 1,500/mm^3;

- Platelet count >=100,000/mm^3;

- Hemoglobin >= 10g/dL;

- Blood urea nitrogen and serum creatinine both =< 1.5 times upper limit of normal

- Total bilirubin both =< 1.5 times ULN;

- SGOT and SGPT both =< 3 times ULN;

- Alkaline phosphatase =< 2 times ULN.

- >=18 years of age;

- Karnofsky Performance Score >= 70;

- Life expectancy >= 8 weeks;

- Negative serum or urine beta-hCG pregnancy test at screening for patients of child
bearing potential;

- Men and women with reproductive potential must agree to use an acceptable method of
birth control (surgical, hormonal or double barrier, ie, condom and diaphragm) during
treatment and for 6 months after completion of treatment;

- Patient or their legal proxy must provide written informed consent prior to
registration on study;

- Residual measurable disease.

Exclusion Criteria:

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study;

- Prior radiation therapy to the brain;

- Prior treatment with Chemotherapy or Targeted agent

- Previous (within last 5 years) or current malignancies at other sites except for
adequately treated basal cell or squamous cell skin cancer in situ carcinoma of the

- (Uncontrolled High blood pressure >150/100

- Common Terminology Criteria Adverse Event 3.0 >= Grade 2 congestive heart failure

- History of myocardial infarction within 6 months;

- History of stroke within 6 months;

- Clinically significant peripheral vascular disease;

- Evidence of bleeding diathesis or coagulopathy;

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to the first dose of bevacizumab or anticipation of need for major surgical
procedure during the course of the study;

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to study enrollment;

- Urine protein/Creatinine ratio >= 2.0 at screening;

- Serious, non-healing wound, ulcer, or bone fracture;

- Inability to comply with study and/or follow-up procedures;

- Glioma showing active intratumoral bleeding;

- Patients on enzyme-inducing anti-epileptic drugs;

- Known Positive HIV-1, hepatitis B surface antigen, or hepatitis C antibody;

- Medications like NSAIDs, antipsychotics, iodides, and ACEI, If they are receiving
them, they must have been discontinued for 7 days prior to initiating lithium;

- Any previous cytotoxic drug therapies, excluding corticosteroids and temozolomide
concurrent with radiation therapy;

- Any known genetic cancer-susceptibility syndromes;

- Acute infection: any active viral, bacterial, or fungal infection that requires
specific therapy.

- Active uncontrolled infection - examples include sexually transmitted disease,
herpes, scrofula, malaria, etc.;

- Fever > 101.5 F0;

- Unstable or severe intercurrent medical conditions such as unstable angina,
uncontrolled arrythmias, Crohn's disease, ulcerative colitis, psoriasis, etc.;

- Implantation of Gliadel wafers at surgery;

- Patients with organ allografts; and

- Allergies to reagents used in this study.

Type of Study:


Study Design:

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

Outcome Measure:

Time to Tumor Progression

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Deborah Gruber, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

New York University Cancer Institute


United States: Institutional Review Board

Study ID:

NYU 07-712



Start Date:

May 2010

Completion Date:

April 2015

Related Keywords:

  • Brain Cancer
  • brain tumor
  • brain cancer
  • glioma
  • Brain Neoplasms
  • Glioma



Overlook HospitalSummit, New Jersey  07902-0220
New York University Clinical Cancer CenterNew York, New York  10016