A Study Using Radiation Therapy and Temozolomide to Treat Glioblastoma in Patients Over 70

A Phase I/ II Study of Hypofractionated Radiotherapy With Concurrent Temozolomide Followed by Adjuvant Temozolomide in Patients Over 70 Years Old With Newly Diagnosed Glioblastoma

In this study we propose to determine outcomes of patients age 70 or older treated with radiation over 2 weeks given with temozolomide 75 mg/m2 daily during radiotherapy and as a post radiation treatment of 150 mg/m2 - 200 mg /m2 for 6 cycles or until the disease progresses.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: Hypofractionated radiotherapy; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • James Graham Brown Cancer Center
      • Contact: Clinical Trials Office; Phone Number: 502-562-3429; Email: ctobcc@louisville.edu
      • Principal Investigator: Shiao Woo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants must have histologically confirmed glioblastoma/gliosarcoma.
2. Tumor o6-methylguanine-DNA-methyltransferase promoter methylation status must be determined
3. Participants must not have had any prior therapy for glioblastoma multiforme including radiation or chemotherapy.
4. Participants must be > 70 years of age.
5. Participants must have life expectancy greater than 6 months.
6. Karnofsky performance status > 60 (ECOG < 2).

7. Patients must have normal organ and marrow function

   • Leukocytes > 3,000/microliter
   • Absolute neutrophil count > 1,500/microliter
   • Platelets > 100,000/microliter
   • Total bilirubin within normal institutional limits 12
   • aspartate aminotransferase test(SGOT)/alanine aminotransferase test(SGPT) < 2.5 X institutional upper limit of normal
   • Creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels about institutional normal
8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Participants may not be receiving any other study agents.
2. Participants may not have had chemotherapy wafer placement at surgery.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide.
4. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5. Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
6. HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with temozolomide. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypofractionated radiotherapy and temozolomide; All subjects will receive treatment as is a single arm study. Two weeks of combined hypofractionated radiotherapy with concurrent temozolomide followed by up to 6 cycles of adjuvant temozolomide treatment.

Radiation: Hypofractionated radiotherapy; Treatment of 3.4 Gy will be given daily 5 days per week over 2 weeks.; Drug: Temozolomide; During concomitant phase Temozolomide will be administered orally at 75 mg/m2 for 2 weeks concomitant with radiotherapy. During the adjuvant phase Temozolomide will be administered orally at 150 mg/m2 on days 1 through day 5 of each 28 day cycle for a maximum of 6 cycles.; Other Names: brand name Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who stop treatment due to CTCAE grade 3 or above toxicities	If < 4 out of 10 patients in the initial analysis stop treatment due to toxicity it can proceed to phase II.	4 weeks after radiation therapy - month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		from study enrollment to date of death or up to approximately 5 years
Quality of Life	Quality of life will be measured by Fact-BR assessment.	7 months after enrollment
The number of patients to complete RT+TMZ and a minimum of 3 of the 6 planned cycles of adjuvant chemotherapy		7 months after enrollment

Collaborators and Investigators

• Sponsor: University of Louisville
• Collaborators: James Graham Brown Cancer Center
• Investigators: Principal Investigator: Shiao Woo, MD, James Graham Brown Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: October 10, 2013
• First Submitted That Met QC Criteria: November 14, 2013
• First Posted (Estimate): November 15, 2013

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: BCC-NEU-13 GB70