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Hypofractionated Intensity-Modulated Radiation Therapy With Temozolomide and Bevacizumab for Glioblastoma Multiforme

Study Purpose

The purpose of this study is to find out whether Hypofractionated Intensity-Modulated Radiation Therapy (Hypo-IMRT) combining with temozolomide chemotherapy can be safely given with a targeted agent, bevacizumab, and how effective this study treatment will be in controlling your brain tumor.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Histologically confirmed diagnosis of WHO grade IV primary malignant glioma (GBM or gliosarcoma).
  • - Age ≥ 18 years at the time of study registration.
  • - Karnofsky Performance Scale ≥ 60% - Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9.0 g/dl, platelets ≥ 100,000 cells/ mm3.
  • - Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal.
  • - Signed informed consent approved by the Institutional Review Board.
  • - Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of study entry.
Study treatment should be initiated > 28 days following the last surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity)

Exclusion Criteria:

  • - Life expectancy of less than 12 weeks.
  • - Prior treatment, including radiation therapy or chemotherapy, for GBM with the exception of surgery (Gliadel Wafers are allowed at the time of surgery) - Active malignancy, with the exception of superficial basal cell and/or superficial squamous (skin) cell, or carcinoma in situ of the cervix.
  • - Active infection requiring IV antibiotics.
  • - Pregnant or breast feeding.
  • - International normalized ratio (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 × the upper limit of normal (ULN) (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject.
Therapeutic anticoagulation is permitted.
  • - Evidence of ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) v.
3 grade 2 CNS hemorrhage (CNS hemorrhage when medical intervention indicated), but grade 1 CNS hemorrhage (asymptomatic radiographic findings on the baseline brain CT or MRI only) is allowed. Punctate hemorrhage or the presence of hemosiderin is not considered a Grade 1 event for the purpose of this study. )
  • - Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg) - Prior history of hypertensive crisis or hypertensive encephalopathy.
  • - Current New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  • - History of myocardial infarction or unstable angina within 6 months prior to enrollment.
  • - History of stroke or transient ischemic attack within 6 months prior to enrollment.
  • - Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to enrollment.
  • - History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to enrollment.
  • - Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or anticipation of need for major surgical procedure during the course of the study.
  • - Core needle biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment.
  • - History of abdominal fistula or gastrointestinal perforation within 6 months prior to enrollment.
  • - Serious, non-healing wound, active ulcer, or untreated bone fracture.
  • - Proteinuria as demonstrated by a Urine protein-creatinine ratios (UPC) ratio ≥ 1.0 at screening (Appendix A).
- Known hypersensitivity to any component of bevacizumab

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01209442
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Colorado, Denver
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Douglas Ney, M.D
Principal Investigator Affiliation University of Colorado, Denver
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma Multiforme
Additional Details

This is a pilot phase II trial of the combination of concurrent hypofractionated IMRT (60 Gy/2 weeks), temozolomide and bevacizumab followed by 6 cycles of adjuvant bevacizumab and temozolomide in patients with grade IV malignant gliomas (glioblastoma and gliosarcoma). The study will have survival and toxicity endpoints.

Arms & Interventions

Arms

Experimental: RT with Temozolomide and Bevacizumab

Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily TMZ at 75 mg/m2 qd concurrent with IMRT (including weekends and holidays). Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Day 1 and the 1st Fx of IMRT must start on the same day. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab therapy, patients will have a brain MRI and if there is no evidence of disease progression, patients will receive 6 cycles of Bevacizumab and TMZ. Beginning a minimum of 28 days after the last radiation treatment the bevacizumab will be dosed at 10 mg/kg on day 1 and day 15 of each cycle. TMZ will be given at 150-200 mg/m2 qd on days 1-5 of each cycle. Each cycle is 28 days.

Interventions

Drug: - Bevacizumab

Bevacizumab will be administered at 10 mg/kg on day 1 and day 15. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab, patients will receive 6 cycles of Bevacizumab.

Drug: - Temozolomide

Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx) and daily temozolomide at 75 mg/m2 qd concurrent with IMRT. Four to six weeks following completion of concurrent IMRT, TMZ and bevacizumab, temozolomide will be given at 150-200 mg/m2 qd on days 1-5 of each cycle.

Radiation: - RT (Radiation Therapy)

Patients will be treated with hypofractionated IMRT (60 Gy in 10 Fx)

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Aurora, Colorado

Status

Address

University of Colorado Denver, University of Colorado Cancer Center

Aurora, Colorado, 80045