Clinical trial NCT01985087: A Study Using Radiation Therapy and Temozolomide to Treat Glioblastoma in Patients Over 70
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: James Graham Brown Cancer Center
First posted: 2013-11-15
Enrollment: 18
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients who stop treatment due to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or above toxicities..
timeFrame: baseline, 14-28 days post-surgery, 4 weeks post chemo-radiation therapy, 1, 2, 3, 4, 5, and 6 months post Radiation Therapy
measure: Overall survival
timeFrame: From date of intervention until the date of first documented disease progression or death, the date of study discontinuation (e.g. toxicity, PI decision) or death from any cause, whichever is first, assessed up to 100 months.
Secondary outcomes:
measure: Estimate progression-free survival (PFS)
timeFrame: From date of intervention until the date of first documented disease progression or death, the date of study discontinuation (e.g. toxicity, PI decision) or death from any cause, whichever is first, assessed up to 100 months.
measure: Tolerability (feasibility) of hypo-fractionated radiaton therapy and Temozolomide
timeFrame: From date of intervention until the date of first documented disease progression or death, the date of study discontinuation (e.g. toxicity, PI decision) or death from any cause, whichever is first, assessed up to 100 months.
Other outcomes:
measure: Explore association of Overall Survival (OS) and Progression Free Survival (PFS) with 06-methylguanine-DNA methyltransferase gene (MGMT) methylation status
timeFrame: From date of intervention until the date of first documented disease progression or death, the date of study discontinuation (e.g. toxicity, PI decision) or death from any cause, whichever is first, assessed up to 100 months.
measure: Explore changes in quality of life (QOL)
timeFrame: 14-28 days after surgery then within 4 weeks from end of chemotherapy-radiation then 1,4, and 6 months post initiation of adjuvant treatment
Locations:
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
Study officials:
affiliation: James Graham Brown Cancer Center
name: Shiao Woo, MD
role: PRINCIPAL_INVESTIGATOR
References: