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

NCT ID: NCT01105702

Last Updated: 2016-08-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2015-04-30

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.

Conditions

Brain Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Temozolomide

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Lithium Carbonate

Intervention Type: DRUG

Radiation

Intervention Type: RADIATION

Interventions

Temozolomide

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Lithium Carbonate

Intervention Type: DRUG

Radiation

Intervention Type: RADIATION

Other Intervention Names

Temodar; Avastin; Lithobid

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Atlantic Health System

OTHER

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deborah Gruber, MD

Role: PRINCIPAL_INVESTIGATOR

New York University Cancer Institute

Locations

Overlook Hospital

Summit, New Jersey, United States

New York University Clinical Cancer Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20231676 (View on PubMed)

Other Identifiers

NYU 07-712

Identifier Type: -

Identifier Source: org_study_id