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

July 6, 2016 updated by: NYU Langone Health

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
    • New York
      • New York, New York, United States, 10016
        • New York University Clinical Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Temodar
Drug: Bevacizumab
Other Names:
  • Avastin
Radiation: Radiation
Drug: Lithium Carbonate
Other Names:
  • Lithobid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to 50 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Overall Survival (OS)
Time Frame: Up to 50 months
OS defined as time from diagnosis to most recent follow up or death.
Up to 50 months
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
The whole time while on treatment and 30 days after the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

Genentech, Inc.
Atlantic Health System

Investigators

  • Principal Investigator: Deborah Gruber, MD, New York University Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (ACTUAL)

April 1, 2014

Study Completion (ACTUAL)

April 1, 2015

Study Registration Dates

First Submitted

April 12, 2010

First Submitted That Met QC Criteria

April 15, 2010

First Posted (ESTIMATE)

April 16, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

August 4, 2016

Last Update Submitted That Met QC Criteria

July 6, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NYU 07-712

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Brain Cancer

Clinical Trials on Temozolomide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Canada

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe