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

Brain Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01105702
• Other study ID #: NYU 07-712
• Status: Terminated
• Phase: Phase 2
• First received: April 12, 2010
• Last updated: October 5, 2015
• Start date: May 2010
• Est. completion date: April 2015

Study information

• Verified date: October 2015
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: April 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Cancer
• Brain Neoplasms

Intervention

Drug:
• Temozolomide

• Bevacizumab

• Lithium Carbonate

Radiation:
• Radiation

Locations

Country	Name	City	State
United States	New York University Clinical Cancer Center	New York	New York
United States	Overlook Hospital	Summit	New Jersey

Sponsors (3)

Lead Sponsor	Collaborator
New York University School of Medicine	Atlantic Health System, Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Progression-Free Survival (PFS)	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	No
Secondary	Median Overall Survival (OS)	OS defined as time from diagnosis to most recent follow up or death.	Up to 50 months	No
Secondary	Number of Patients With Grade 3 or 4 Adverse Events	Adverse events evaluated per CTCAE 3	The whole time while on treatment and 30 days after the treatment	Yes