Analyzing Pulsed Reduced Dose Radiotherapy in Upfront Glioblastoma

NCT04747145 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: PRO00039277
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The primary protocol objective is to assess the impact of substituting pulsed reduced dose radiotherapy (pRDR) for standard radiation therapy in the upfront treatment of glioblastoma (GBM) on disease progression.

Conditions

Glioblastoma

Keywords

pulsed reduced dose radiotherapy; glioblastoma; pRDR

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  This outcome measure is the number of subjects whose disease has not progressed using the Macdonald Response Criteria, which has the following classifications: complete response, partial response, stable disease and progression.

  Six months

Study Arms (1)

Pulsed reduced dose-rate radiotherapy

EXPERIMENTAL

Chemoradiation, adjuvant chemotherapy.

Device: Radiation; Drug: Concurrent Chemotherapy (Temozolomide); Drug: Adjuvant Chemotherapy (Temozolomide)

Interventions

Radiation DEVICE

60 Gy to be delivered over 30 daily treatments in six weeks. Chemoradiation is to start no sooner than 3 weeks after surgery and not later than 8 weeks.

Also known as: Pulsed Reduced Dose Radiotherapy, pRDR

Pulsed reduced dose-rate radiotherapy

Concurrent Chemotherapy (Temozolomide) DRUG

75mg/m\^2 x 42 days (concurrent chemotherapy with radiation). Chemoradiation is to start no sooner than 3 weeks after surgery and not later than 8 weeks.

Also known as: TMZ, Temodar

Pulsed reduced dose-rate radiotherapy

Adjuvant Chemotherapy (Temozolomide) DRUG

Starting no sooner than 4 weeks after completion of chemoradiation, 150-200mg/m\^2, days 1-5 of 28-day cycle, for minimum of six cycles and up to 12 cycles.

Also known as: TMZ, Temodar

Pulsed reduced dose-rate radiotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntary written consent must be given before performance of any study-related procedure that is not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female or male subjects ≥ 18 years old at the time of informed consent.
• Histologically confirmed new diagnosis of GBM according to updated World Health Organization (WHO) classification criteria.
• Supratentorial tumor location.
• Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection and biopsy-only patients are all acceptable).
• Planned treatment with adjuvant/maintenance TMZ (150 to 200 mg/m\^2 daily x 5 d, q 28 days).
• All patients with sufficient tissue must have had tissue submitted for O6-Methylguanine-DNA Methyltransferase (MGMT) promoter methylation determination prior to enrollment.
• Karnofsky Performance Status Scale ≥ 70.
• Life expectancy greater than at least three months.
• Study start date at least three weeks out from brain surgery.
• Stable or decreasing dose of corticosteroids for the last seven days prior to enrollment, if applicable.
• Complete blood count (CBC) /differential obtained within 28 days prior to registration, with adequate bone marrow function defined as follows: absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3; platelets ≥ 100,000 cells/mm\^3; hemoglobin ≥ 10.0 g/dL. (Note: the use of transfusion or other intervention to achieve Hgb ≥10.0 g/dL is acceptable.)
• Female subjects who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR

You may not qualify if:

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of three years. (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• Recurrent or multifocal malignant gliomas.
• Any site of distant disease (i.e., leptomeningeal disease or drop metastases from the GBM tumor site).
• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
• Severe, active comorbidity, defined as follows:
• Unstable angina at registration.
• Transmural myocardial infarction within the last six months prior to registration.
• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of ≥ 2 mm using the analysis of an EKG performed within 28 days prior to registration. (Note: EKG to be performed only if clinical suspicion of cardiac issue.)
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to.
• Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration.
• Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
• End-stage renal disease (i.e., on dialysis or dialysis has been recommended).
• Patents treated on any other therapeutic clinical protocols within 30 days prior to registration.
• Inability to undergo MRI.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Radiotherapy; Temozolomide; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Drug Therapy

Study Officials

• Michael Straza, MD, PhD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 6, 2021
• First Posted: February 10, 2021
• Study Start: June 3, 2021
• Primary Completion: March 5, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)