Subventricular Zone (SVZ) and Temozolomide in Glioblastoma Multiforme

NCT02177578 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: J1426IRB00031466
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

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.

Conditions

Glioblastoma Multiforme

Keywords

Subventricular Zone; progenitor cell; radiation therapy; temozolomide

Outcome Measures

Primary Outcomes (1)

• Change from Baseline to Initial Progression

  Compare progression-free survival in patients receiving subventricular zone irradiation for newly diagnosed glioblastoma multiforme versus patients receiving a radiation treatment plan that does not intentionally include this area.

  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 (12)

• Progression Free Survival

  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

• Rate of Distant Brain Progression

  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

• Multifocal Disease Development

  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

• Location of Disease Progression

  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

• Neurocognitive Function Change from Baseline

  Baseline and then in follow-up post radiation treatment at 6 months, 12 months and 24 months

Study Arms (2)

Temozolomide plus radiation therapy to the tumor and SVZ

EXPERIMENTAL

Patients will be scheduled to receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle). Patients will receive 60 Gy of radiation therapy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows: Initial treatment plan will include the tumor bed and MRI changes based on T1 post gadolinium series and FLAIR series, plus the bilateral subventricular zone Will be prescribed to 46 Gy in 2 Gy fractions Cone down treatment plan will include the tumor bed, areas of contrast enhancement on T1 post gadolinium series MRI plus the ipsilateral subventricular zone Will be prescribed to 14 Gy in 2 Gy fractions

Drug: Temozolomide; Radiation: Subventricular Zone radiation

Temozolomide and neural progenitor cell sparing radiation

ACTIVE COMPARATOR

Patients will receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle). Patients will receive 60 Gy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows: Initial treatment plan will include the tumor bed and MRI abnormalities based on T1 post gadolinium series and FLAIR series. Will be prescribed to 46 Gy in 2 Gy fractions Cone down treatment plan will include the tumor bed and MRI changes based on T1 post gadolinium series. Will be prescribed to 14 Gy in 2 Gy fractions

Drug: Temozolomide; Radiation: Neural Progenitor Cell Sparing radiation

Interventions

Temozolomide DRUG

Patients will be scheduled to receive continuous daily temozolomide (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy), followed by 6 cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28 day cycle).

Temozolomide and neural progenitor cell sparing radiation; Temozolomide plus radiation therapy to the tumor and SVZ

Subventricular Zone radiation RADIATION

Patients will receive 60 Gy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows: Initial treatment plan: Will be prescribed to 46 Gy in 2 Gy fractions Cone down treatment plan: Will be prescribed to 14 Gy in 2 Gy fractions

Temozolomide plus radiation therapy to the tumor and SVZ

Neural Progenitor Cell Sparing radiation RADIATION

Patients will receive 60 Gy in 30 fractions, 5 days per week using IMRT. The target delineation and treatment volumes will be as follows: Initial treatment plan: Will be prescribed to 46 Gy in 2 Gy fractions Cone down treatment plan: Will be prescribed to 14 Gy in 2 Gy fractions

Temozolomide and neural progenitor cell sparing radiation

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Reading Health System Foundation: collaborator

Study Sites (3)

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Location

The SKCCC at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Suburban Hospital

Bethesda, Maryland, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kristin Redmond, M.D.

  The SKCCC at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: June 27, 2014
• Study Start: July 8, 2014
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (3)