Carbon C 11 Temozolomide, PET, and MRI in Studying Tumor Blood Vessels in Patients with Recurrent Glioblastoma Receiving Bevacizumab and Temozolomide

Status: Active

Description

This pilot clinical trial studies carbon C 11 temozolomide, positron emission tomography (PET), and magnetic resonance imaging (MRI) in studying tumor blood vessels in patients with brain tumors that have come back and are receiving bevacizumab and temozolomide. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with bevacizumab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Since anti-VEGF agents also affect normal blood vessels in the brain, they may inhibit the way temozolomide is delivered to the tumor. Using a radioactive substance, such as carbon C 11 temozolomide, PET, and MRI may allow doctors to evaluate the changes in tumor blood flow, blood volume, and how receptive blood vessels are while also measuring how much temozolomide is in the brain.

Eligibility Criteria

Inclusion Criteria

  • Participants must have histologically confirmed glioblastoma and evidence of recurrence > 2 months since last cycle of temozolomide or other alkylating agent; patients with low-grade tumors who have progressed to glioblastoma are eligible
  • Patients must have received prior temozolomide or an alkylating agent (ex. lomustine [CCNU]/carmustine [BCNU])
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm
  • Only patients for whom their neuro-oncologist has planned to give bevacizumab and temozolomide 50mg/m^2/day as part of their treatment are eligible for this study
  • Life expectancy of greater than 3 months
  • Karnofsky performance status > 60
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for subjects with creatinine levels about institutional normal
  • Patient must be able to undergo MRI and PET scans
  • Patients must be maintained on a stable corticosteroid regimen for 5 days prior each magnetic resonance (MR)-PET scan
  • The effects of radiolabed temozolomide on the developing human fetus are unknown; for this reason and because radiopharmaceuticals agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide
  • Participants who have already received anti-VEGF or experimental antiangiogenic therapy for glioblastoma
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because radiolabeled temozolomide is a radiopharmaceutical agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiopharmaceutical agents, breastfeeding should be discontinued if the mother is treated with radiopharmaceutical agents; these potential risks may also apply to other agents used in this study.
  • Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with radiolabeled temozolomide. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
  • Patients who are not suitable to undergo MRI or use gadolinium contrast due to: * Claustrophobia * Presence of metallic objects or implanted medical devices in body (i.e. cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) * Sickle cell disease * Renal failure * Reduced renal function, as determined by creatinine clearance < 30 mL/min based on a serum creatinine level obtained within 28 days prior to registration

Locations & Contacts

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Elizabeth R. Gerstner
Email: egerstner@partners.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess temozolomide delivery before and after bevacizumab in glioblastoma.

SECONDARY OBJECTIVES:

I.To explore the link between flow, permeability, and tumor temozolomide retention.

Ia. Measure tumor blood flow with MRI perfusion and compare with temozolomide retention.

Ib. Estimate permeability from K^trans MRI measurements and compare with temozolomide retention.

OUTLINE:

Patients receive standard treatment comprising temozolomide orally (PO) daily on days 1-28 and bevacizumab intravenously (IV) on days 14 and 28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive carbon C 11 temozolomide IV over 30 seconds and then undergo PET and MRI on days 7-13 and on day 15 of course 1.

After completion of study treatment, patients are followed up every 3 months for 3 years.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Elizabeth R. Gerstner

Trial IDs

Primary ID 13-322
Secondary IDs NCI-2014-00321
Clinicaltrials.gov ID NCT01987830