Clinical trial NCT02177578: Subventricular Zone (SVZ) and Temozolomide in Glioblastoma Multiforme
Official title: A Randomized Phase II Study of Subventricular Zone (SVZ) Irradiation Plus Temozolomide in Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Subventricular Zone
progenitor cell
radiation therapy
temozolomide
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Reading Health System Foundation
First posted: 2014-06-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study patients will be treated with 6 weeks of radiation therapy plus temozolomide chemotherapy according to the standard of care. However, the radiation treatment plan will be modified to deliver an higher than routine radiation dose to the subventricular zone which is an area of the brain that contains stem cells that some scientists believe may contribute to glioblastoma recurrence. The purpose of the study is to see if the tumor is controlled for a longer period of time in patients treated with this modified radiation technique than it is in patients treated with standard radiation therapy plus temozolomide chemotherapy.

Detailed description: There is pre-clinical data to suggest that neural progenitor cells in the subventricular zone may play a role in glioblastoma recurrence. Retrospective studies in humans suggest potentially improved survival in patients who received high doses of radiation to the subventricular zone when compared with patients who received lower radiation doses to this area. The purpose of this study is to prospectively examine progression free survival in patients with newly diagnosed glioblastoma treated with adjuvant temozolomide plus a radiation treatment plan which intentionally prescribes radiation dose to both the tumor and the subventricular zone compared to patients treated with standard radiation therapy. 3 patients out of every 4 will be treated with the modified study radiation treatment and 1 patient out of every 4 will received a more standard radiation treatment plan.

Eligibility criteria: Inclusion Criteria:

* Patient must have newly diagnosed, histologically confirmed GBM.
* Patient must have undergone gross total resection, subtotal resection, or biopsy with the extent of resection determined by the treating neurosurgeon, and must begin radiation within 12 weeks of this procedure.
* Patients must not have received previous irradiation to the brain.
* Patient must be at least 18 years of age since the diagnosis of GBM in patients younger than 18 is rare and accurate evaluation of neurocognitive function would require a different battery of examinations than employed in this study.
* ECOG performance status 0-2 (Karnofsky \>60%; see Appendix A).
* Patient must be scheduled to receive temozolomide concurrent with and following radiation (temozolomide may be started late due to insurance reasons, insufficient counts, or other reasons).
* If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 12 weeks following the study. Should a women become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.
* Patient must have the ability to understand and the willingness to sign a written informed consent document.
* All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines.
* Radiation therapy must begin within 12 weeks of surgery.

Exclusion Criteria:

* No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 2 years.
* Patients with 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 will be excluded.
* Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. This applies to any woman who has not experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Male subjects must also agree to use effective contraception for the same period as above.
* Use of Avastin or another VEG-F inhibitor prior to progression is not permitted.

Primary outcomes:
measure: Change from Baseline to Initial Progression
timeFrame: MRIs and clinical evaluations will be completed starting at the end of radiation therapy, at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, and at 24 months to identify the time of initial disease progression
Secondary outcomes:
measure: Progression Free Survival
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
measure: Rate of Distant Brain Progression
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
measure: Multifocal Disease Development
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
measure: Location of Disease Progression
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
measure: Neurocognitive Function Change from Baseline
timeFrame: Baseline and then in follow-up post radiation treatment at 6 months, 12 months and 24 months
measure: Composite Cognitive Function Change from Baseline
timeFrame: Baseline and then in follow-up post radiation treatment at 6 months, 12 months and 24 months
measure: Cognitive Function Change from Baseline
timeFrame: Baseline and then in follow-up post radiation treatment at 6 months, 12 months and 24 months
measure: Quality of Life Change from Baseline
timeFrame: Baseline and then in follow-up post radiation treatment at 6 months, 12 months and 24 months
measure: Acute and Late Toxicity Change from Baseline
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
measure: Pathologically Confirmed Necrosis Change from Baseline
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
measure: Pseudo-Progression Change from Baseline
timeFrame: One year post completion of radiation treatment
measure: Overall Survival
timeFrame: MRIs and clinical evaluations will be performed 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 24 months following completion of of radiation therapy
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: The SKCCC at Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
Study officials:
affiliation: The SKCCC at Johns Hopkins
name: Kristin Redmond, M.D.
role: PRINCIPAL_INVESTIGATOR
References: