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

Sponsor

University of Wisconsin, Madison (Other)

Overall Status

Recruiting

CT.gov ID

NCT01743950

Collaborator

Genentech, Inc. (Industry), National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

143.9

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioma	Drug: Bevacizumab Radiation: PRDR	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 3, 2012

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bevacizumab-naïve with recurrent glioblastoma 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 glioblastoma 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 anaplastic 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 anaplastic 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

Outcome Measures

Primary Outcome Measures

Overall survival [end of study, which will be an average of 12 months]
time of first dose of PDRD+ Bevacizumab until time of death

Secondary Outcome Measures

Incidence of Adverse Events [up 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.
Incidence of Late Toxicities [from 90 days post radiotherapy until time of death]
Late toxicity that is likely attributable to re-irradiation or bevacizumab will be recorded.
progression free survival [at 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 Mini Mental State Exam (MMSE) Score [baseline 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.
Change in Participant Reported FACT-BR Score [baseline 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 Participant Reported FACIT-F Score [baseline 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.
Change in Karnofsky Performance Status [baseline 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnose of a grade WHO grade III or IV glioma
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 > 6months post completion of initial radiation therapy
Bevacizumab exposed patients must be > 3months 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
May not be on full dose anti-coagulation therapy, Low molecular weight heparin is ok
Uncontrolled hypertension (>140/90mmHg)
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

University of Wisconsin, Madison
Genentech, Inc.
National Cancer Institute (NCI)

Investigators

Principal Investigator: Steve Howard, MD, University of Wisconsin, Madison
Principal Investigator: H. Ian Robins, MD, Ph.D, University of Wisconsin, Madison