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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech
Ohio State University
Atlantic Health System
Information provided by:
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01105702
First received: April 12, 2010
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

This is an open-label, Phase II study to estimate the effect on time to tumor progression and safety in patients with newly diagnosed high grade glioma.


Condition Intervention Phase
Brain Cancer
Drug: Temozolomide
Drug: Bevacizumab
Drug: Lithium
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:
  • Time to Tumor Progression [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: May 2010
Estimated Study Completion Date: December 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temozolomide, Bevacizumab, Lithium, Radiation

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 will be added 29 days post surgery.

Treatment Cycle 2-7 (28-day cycles)

  • 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 treatment at 300 mg PO BID; increase dose every 7 days by 300 mg to goal total dose of 1200 mg per day
  • Magnetic Resonance Imaging is performed after every 2 cycles
Drug: Temozolomide
Other Name: Temodar
Drug: Bevacizumab
Other Name: Avastin
Drug: Lithium
Lithobid
Radiation: Radiation

Detailed Description:

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).

  Eligibility

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

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 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.
  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

Locations
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
Ohio State University
Atlantic Health System
Investigators
Principal Investigator: Deborah Gruber, MD New York University Cancer Institute
  More Information

No publications provided

Responsible Party: Deborah Gruber, MD, New York University Cancer Institute
ClinicalTrials.gov Identifier: NCT01105702     History of Changes
Other Study ID Numbers: NYU 07-712
Study First Received: April 12, 2010
Last Updated: February 26, 2014
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on September 16, 2014