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

• ClinicalTrials.gov Identifier: NCT01743950
• Recruitment Status: Recruiting
• First Posted: December 6, 2012
• Last Update Posted: November 18, 2022
• Sponsor: University of Wisconsin, Madison
• Collaborators: Genentech, Inc.; National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Wisconsin, Madison

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 (Clinical Trial)
• Estimated 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: December 3, 2012
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2024

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: re-irradiation

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 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 :

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

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

Criteria

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

Contacts and Locations

Contacts

Contact: Diana Trask, BS; 608-263-9528; trask@humonc.wisc.edu

Contact: Nick Anger, BS; 608-262-8649; anger@humonc.wisc.edu

Locations

United States, Wisconsin

University of Wisconsin Hospital and Clinics; Recruiting

Madison, Wisconsin, United States, 53792

Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu

Principal Investigator: Steve Howard, MD

Principal Investigator: H. Ian Robins, MD, Ph.D

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

More Information

Additional Information:

University of Wisconsin Carbone Cancer Center 

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01743950
• Other Study ID Numbers: CO11374; NCI-2012-02775 ( Registry Identifier: NCI Trial ID ); 2012-0648 ( Other Identifier: Institutional Review Board ); 2017-0683 ( Other Identifier: Institutional Review Board ); A533300 ( Other Identifier: UW Madison ); SMPH\HUMAN ONCOLOGY\HUMAN ONCO ( Other Identifier: UW Madison ); Protocol Version 10/14/2020 ( Other Identifier: UW Madison )
• First Posted: December 6, 2012
• Last Update Posted: November 18, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by University of Wisconsin, Madison:

Glioblastoma; anaplastic glioma

Additional relevant MeSH terms:

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors