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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01105702
Recruitment Status : Terminated (Due to slow accrual)
First Posted : April 16, 2010
Results First Posted : November 6, 2015
Last Update Posted : August 4, 2016
Genentech, Inc.
Atlantic Health System
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE April 12, 2010
First Posted Date  ICMJE April 16, 2010
Results First Submitted Date  ICMJE October 5, 2015
Results First Posted Date  ICMJE November 6, 2015
Last Update Posted Date August 4, 2016
Study Start Date  ICMJE May 2010
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2015)
Median Progression-Free Survival (PFS) [ Time Frame: Up to 50 months ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2010)
Time to Tumor Progression [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2015)
  • Median Overall Survival (OS) [ Time Frame: Up to 50 months ]
    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 ]
    Adverse events evaluated per CTCAE 3
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Temodar (Temozolomide), Bevacizumab, Lithium and Radiation for High Grade Glioma
Official Title  ICMJE Temozolomide, Bevacizumab, Lithium and Radiation Treatment for Newly Diagnosed High Grade Glioma: A Phase II Study
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Cancer
Intervention  ICMJE
  • Drug: Temozolomide
    Other Name: Temodar
  • Drug: Bevacizumab
    Other Name: Avastin
  • Drug: Lithium Carbonate
    Other Name: Lithobid
  • Radiation: Radiation
Study Arms  ICMJE 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
  • Drug: Bevacizumab
  • Drug: Lithium Carbonate
  • Radiation: Radiation
Publications * Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 26, 2014)
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2010)
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01105702
Other Study ID Numbers  ICMJE NYU 07-712
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NYU Langone Health
Study Sponsor  ICMJE NYU Langone Health
Collaborators  ICMJE
  • Genentech, Inc.
  • Atlantic Health System
Investigators  ICMJE
Principal Investigator: Deborah Gruber, MD New York University Cancer Institute
PRS Account NYU Langone Health
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP