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

NCT01743950 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 6 other identifiers: 2017-0683NCI-2012-027752012-0648A533300SMPH\HUMAN ONCOLOGY\HUMAN ONCOProtocol Version 10/14/2020
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioma

Keywords

Glioblastoma; anaplastic glioma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Incidence of Adverse Events

  data collected up to 18 months

• Incidence of Late Toxicities

  data collected up to 18 months

• Progression Free Survival

  estimated to be an average of 12 months (the estimated mean follow-up time)

• Change in Mini Mental State Exam (MMSE) Score

  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

  data collected baseline and then approximately every 2 months for 8 months (participants did not provide data after 8 months)

Study Arms (4)

Bevacizumab-naïve with recurrent IDH wildtype high grade glioma

ACTIVE COMPARATOR

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Drug: Bevacizumab; Radiation: PRDR

Bevacizumab-exposed with refractory recurrent IDH wildtype high grade glioma

ACTIVE COMPARATOR

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Drug: Bevacizumab; Radiation: PRDR

Bevacizumab-naïve with recurrent IDH mutant glioma

ACTIVE COMPARATOR

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Drug: Bevacizumab; Radiation: PRDR

Bevacizumab-exposed with recurrent IDH mutant glioma

ACTIVE COMPARATOR

27fractions over 5.5weeks of PRDR radiation with bevacizumab followed by adjuvant bevacizumab until time of progression

Drug: Bevacizumab; Radiation: PRDR

Interventions

Bevacizumab DRUG

10mg/kg every 2weeks.

Bevacizumab-exposed with recurrent IDH mutant glioma; Bevacizumab-exposed with refractory recurrent IDH wildtype high grade glioma; Bevacizumab-naïve with recurrent IDH mutant glioma; Bevacizumab-naïve with recurrent IDH wildtype high grade glioma

PRDR RADIATION

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.

Also known as: re-irradiation

Bevacizumab-exposed with recurrent IDH mutant glioma; Bevacizumab-exposed with refractory recurrent IDH wildtype high grade glioma; Bevacizumab-naïve with recurrent IDH mutant glioma; Bevacizumab-naïve with recurrent IDH wildtype high grade glioma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

Bevacizumab; Re-Irradiation

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Retreatment

Limitations and Caveats

Study was terminated early per slow accrual and is underpowered for meaningful interpretation.

Results Point of Contact

• Title: Brett Morris, MD, PhD
• Organization: University of Wisconsin - Madison

bmorris@humonc.wisc.edu

(608) 265-5094

Study Officials

• Steve Howard, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• H. Ian Robins, MD, Ph.D

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: December 6, 2012
• Study Start: December 3, 2012
• Primary Completion: December 24, 2024
• Study Completion: December 24, 2024
• Last Updated: March 25, 2026
• Results First Posted: March 25, 2026

Record last verified: 2026-01

Locations

US (1)