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

Phase 2
Terminated
Conditions
Glioma
Interventions
Radiation: PRDR
Registration Number
NCT01743950
Lead Sponsor
University of Wisconsin, Madison
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
49
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bevacizumab-exposed with refractory recurrent IDH wildtype high grade gliomaPRDR27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-naïve with recurrent IDH wildtype high grade gliomaBevacizumab27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-naïve with recurrent IDH mutant gliomaPRDR27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-exposed with recurrent IDH mutant gliomaPRDR27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-naïve with recurrent IDH wildtype high grade gliomaPRDR27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-exposed with refractory recurrent IDH wildtype high grade gliomaBevacizumab27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-exposed with recurrent IDH mutant gliomaBevacizumab27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Bevacizumab-naïve with recurrent IDH mutant gliomaBevacizumab27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression
Primary Outcome Measures
NameTimeMethod
Overall survivalend of study, which will be an average of 12 months

time of first dose of PDRD+ Bevacizumab until time of death

Secondary Outcome Measures
NameTimeMethod
Change in Mini Mental State Exam (MMSE) Scorebaseline and then approximately every 8 weeks for 18 months

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.

progression free survivalat 3 months for bevacizumab exposed patients, at 6 and 12 months for all patients

Progression free survival (PFS) will be defined as the time from the first study treatment to the first occurrence of disease progression or death.

Change in Participant Reported FACIT-F Scorebaseline and then approximately every 8 weeks for 18 months

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.

Incidence of Late Toxicitiesfrom 90 days post radiotherapy until time of death

Late toxicity that is likely attributable to re-irradiation or bevacizumab will be recorded.

Incidence of Adverse Eventsup to 30 days post last dose of bevacizumab

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.

Change in Participant Reported FACT-BR Scorebaseline and then approximately every 8 weeks for 18 months

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.

Change in Karnofsky Performance Statusbaseline and then approximately every 8 weeks for 18 months

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.

Trial Locations

Locations (1)

University of Wisconsin Hospital and Clinics

🇺🇸

Madison, Wisconsin, United States

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