Temodar (Temozolomide), Bevacizumab, Lithium and Radiation for High Grade Glioma

This study has been terminated.
(Due to slow accrual)
Genentech, Inc.
Atlantic Health System
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
First received: April 12, 2010
Last updated: October 5, 2015
Last verified: October 2015
This pilot phase II trial studies how well giving temozolomide, bevacizumab, lithium carbonate, and radiation therapy works in treating patients with newly diagnosed high grade glioma.

Condition Intervention Phase
Brain Cancer
Drug: Temozolomide
Drug: Bevacizumab
Drug: Lithium Carbonate
Radiation: Radiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Temozolomide, Bevacizumab, Lithium and Radiation Treatment for Newly Diagnosed High Grade Glioma: A Phase II Study

Resource links provided by NLM:

Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Median Progression-Free Survival (PFS) [ Time Frame: Up to 50 months ] [ Designated as safety issue: No ]
    PFS defined as time from date of diagnosis to most recent follow up, disease progression, or death. Disease progress defined as either clinical deterioration or radiographic progressive disease on magnetic resonance imaging (MRI) per updated response assessment in neuro-oncology criteria (Wen, et al).

Secondary Outcome Measures:
  • Median Overall Survival (OS) [ Time Frame: Up to 50 months ] [ Designated as safety issue: No ]
    OS defined as time from diagnosis to most recent follow up or death.

  • Number of Patients With Grade 3 or 4 Adverse Events [ Time Frame: The whole time while on treatment and 30 days after the treatment ] [ Designated as safety issue: Yes ]
    Adverse events evaluated per CTCAE 3

Enrollment: 28
Study Start Date: May 2010
Study Completion Date: April 2015
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TBL/RT

Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
Drug: Temozolomide
Other Name: Temodar
Drug: Bevacizumab
Other Name: Avastin
Drug: Lithium Carbonate
Other Name: Lithobid
Radiation: Radiation

Detailed Description:
Treatment of high grade glioma (HGG) with anti-angiogenic therapy results in clinical improvement and prolonged progression-free survival (PFS). However, mant patients experience diffuse recurrence and treatment failure. This is a phase II trial testing the feasibility of adding lithium carbonate, previously shown to have anti-invasive properties in HGG, to bevacizumab and chemoradiation following surgical resection of HGG.

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

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 (ULN);
    • 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 cervix;
  • (Uncontrolled High blood pressure >150/100
  • Common Terminology Criteria Adverse Event 3.0 >= Grade 2 congestive heart failure (CHF);
  • 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 nonsteroidal antiinflammatory drugs, antipsychotics, iodides, and angiotensin-converting enzyme inhibitor, 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 degrees Fahrenheit;
  • 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.
  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: NCT01105702

United States, New Jersey
Overlook Hospital
Summit, New Jersey, United States, 07902
United States, New York
New York University Clinical Cancer Center
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Genentech, Inc.
Atlantic Health System
Principal Investigator: Deborah Gruber, MD New York University Cancer Institute
  More Information

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01105702     History of Changes
Other Study ID Numbers: NYU 07-712
Study First Received: April 12, 2010
Results First Received: October 5, 2015
Last Updated: October 5, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
brain tumor
brain cancer

Additional relevant MeSH terms:
Brain Neoplasms
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Lithium Carbonate
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antidepressive Agents
Antimanic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2015