A Phase II Study of Pulse Reduced Dose Rate Radiation Therapy With Bevacizumab

To determine the efficacy of Pulse Reduced Dose Rate (PRDR) radiation when given in 27 fraction over 5.5 weeks with concurrent bevacizumab followed by adjuvant bevacizumab until time of progression in patients with recurrent high grade gliomas (grade III and grade IV). Patients will be placed in 1 of 4 groups based on their histologic diagnosis and prior exposure to bevacizumab.

Study Overview

• Status: Terminated
• Conditions: Glioma
• Intervention / Treatment: Drug: Bevacizumab; Radiation: PRDR

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or molecularly confirmed Grade 3 or 4 glioma, IDH mutant or wildtype, as defined by the 2021 WHO guidelines
• Recurrent disease based on combination of clinical, imaging or histologic confirmation
• Must have previously received radiation and temozolomide to treat their glioma
• Bevacizumab naive patients must be > 5 months post completion of initial radiation therapy
• Bevacizumab exposed patients must be > 3 months post completion of initial radiation therapy
• Age must be >18years, KPS must be greater than 60
• Hematology, chemistry and a urinalysis must meet protocol specified criteria

Exclusion Criteria:

• Pregnant or breastfeeding
• Uncontrolled hypertension (>160/90mmHg)
• Prior malignancy unless treated >1 year prior to study and have been without treatment and disease free for 1 yr
• active second malignancy unless non-melanoma skin cancer or cervical cancer in situ

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bevacizumab-naïve with recurrent IDH wildtype high grade glioma; 27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression	Drug: Bevacizumab; 10mg/kg every 2weeks.; Radiation: PRDR; Daily dose of 2.0gy delivered in .2gy pulses for a total of 54gy over 5.5 weeks and 27 fractions. In the rare instance of the presence of extensive disease requiring essentially whole brain radiation, a total daily dose of 1.8 Gy delivered in .2 Gy pulses for 23 fractions to a total dose of 41.4 Gy will be utilized.; Other Names: re-irradiation
Active Comparator: Bevacizumab-exposed with refractory recurrent IDH wildtype high grade glioma; 27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression	Drug: Bevacizumab; 10mg/kg every 2weeks.; Radiation: PRDR; Daily dose of 2.0gy delivered in .2gy pulses for a total of 54gy over 5.5 weeks and 27 fractions. In the rare instance of the presence of extensive disease requiring essentially whole brain radiation, a total daily dose of 1.8 Gy delivered in .2 Gy pulses for 23 fractions to a total dose of 41.4 Gy will be utilized.; Other Names: re-irradiation
Active Comparator: Bevacizumab-naïve with recurrent IDH mutant glioma; 27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression	Drug: Bevacizumab; 10mg/kg every 2weeks.; Radiation: PRDR; Daily dose of 2.0gy delivered in .2gy pulses for a total of 54gy over 5.5 weeks and 27 fractions. In the rare instance of the presence of extensive disease requiring essentially whole brain radiation, a total daily dose of 1.8 Gy delivered in .2 Gy pulses for 23 fractions to a total dose of 41.4 Gy will be utilized.; Other Names: re-irradiation
Active Comparator: Bevacizumab-exposed with recurrent IDH mutant glioma; 27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression	Drug: Bevacizumab; 10mg/kg every 2weeks.; Radiation: PRDR; Daily dose of 2.0gy delivered in .2gy pulses for a total of 54gy over 5.5 weeks and 27 fractions. In the rare instance of the presence of extensive disease requiring essentially whole brain radiation, a total daily dose of 1.8 Gy delivered in .2 Gy pulses for 23 fractions to a total dose of 41.4 Gy will be utilized.; Other Names: re-irradiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	time of first dose of PRDR+ Bevacizumab until time of death	estimated to be an average of 12 months (the estimated mean follow-up time)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	time of first dose of PDRD+ Bevacizumab until time of death. All changes from baseline assessment will be recorded until 30 days post last dose of bevacizumab, assessed using the NCI CTCAE version 4.0 criteria.	data collected up to 18 months
Incidence of Late Toxicities	Late toxicity that is likely attributable to re-irradiation or bevacizumab will be recorded.	data collected up to 18 months
Progression Free Survival	Progression free survival (PFS) will be defined as the time from the first study treatment to the first occurrence of disease progression or death.	estimated to be an average of 12 months (the estimated mean follow-up time)
Change in Mini Mental State Exam (MMSE) Score	The MMSE survey is a clinician facilitated instrument scored on a scale of 0-30 where scores of 0-17 indicate severe cognitive impairment, 18-23 indicate mild cognitive impairment, and 24-30 indicate no cognitive impairment.	data collected baseline and then approximately every 2 months for 8 months (participants did not provide data after 8 months)
Change in Participant Reported FACT-BR Score	The Functional Assessment of Cancer Therapy - Brain (FACT-BR) instrument is a 50-item survey with each item scored on a 5 point likert scale where 0 is 'not at all' and 4 is 'very much'. The total possible range of scores is 0-200 where higher scores indicate higher quality of life.	data collected baseline and then approximately every 2 months for 8 months (participants did not provide data after 8 months)
Change in Participant Reported FACIT-F Score	The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) instrument is a 13-item survey with each item scored on a 5 point likert scale where 0 is 'not at all' and 4 is 'very much'. The total possible range of scores is from 0-52 where higher scores indicate better quality of life. A score of less than 30 indicates severe fatigue.	data collected baseline and then approximately every 2 months for 8 months (participants did not provide data after 8 months)
Change in Karnofsky Performance Status	The Karnofsky Performance Status measures a cancer patient's ability to perform ordinary tasks. It is score from 0-100 where 0 means a person has died, less than 40 is various degrees of unable to care for oneself, 50-70 is unable to work but can care for personal needs with variable assistance, and 80-100 is able to carry on normal activity with variable symptoms of disease.	baseline and then approximately every 2 months for up to 10 months (data was not collected from participants after 10 months)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI); Genentech, Inc.
• Investigators: Principal Investigator: Steve Howard, MD, University of Wisconsin, Madison; Principal Investigator: H. Ian Robins, MD, Ph.D, University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2012
• Primary Completion (Actual): December 24, 2024
• Study Completion (Actual): December 24, 2024

Study Registration Dates

• First Submitted: November 27, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimated): December 6, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Glioblastoma; anaplastic glioma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Radiotherapy; Retreatment; Bevacizumab; Re-Irradiation
• Other Study ID Numbers: 2017-0683 (Other Identifier: Institutional Review Board); A533300 (Other Identifier: UW Madison); SMPH\HUMAN ONCOLOGY\HUMAN ONCO (Other Identifier: UW Madison); 2012-0648 (Other Identifier: M D Anderson Cancer Center); NCI-2012-02775 (Registry Identifier: NCI Trial ID); Protocol Version 10/14/2020 (Other Identifier: UW Madison)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes