Study Stopped
Lack of Accrual/Enrollment
Dose Escalated MRSI Guided Radiation Therapy in Glioblastoma
Phase II Study of Dose Escalated, Targeted Radiation Therapy Using 3D Magnetic Resonance Spectroscopy Imaging (MRSI) in Newly Diagnosed Glioblastoma
1 other identifier
interventional
1
1 country
1
Brief Summary
In summary, the overall prognosis of glioblastoma (GBM) patients remains poor. Although clinical gains have been achieved in the past, these have been modest, with a majority of patients succumbing to local disease progression within 2 years. New strategies for treatment need to be identified which enhance local control above the current treatment regimen in order to achieve further clinical gains in this disease. Favorable early experience with magnetic resonance spectroscopy imaging (MRSI) demonstrates that metabolic imaging can identify active tumor beyond standard MRI as well as high risk regions at risk for local failure. There is also clinical evidence that limited field dose escalation with either simultaneous integrated boost (SIB) or stereotactic radiosurgery (SRS) is feasible and safe. Coupling these findings provide the rationale for this proposed Phase II trial designed to define efficacy and toxicity of the novel treatment approach of whole brain volumetric 3D MRSI guided dose-escalated radiation therapy (RT) in newly diagnosed GBM patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2015
Shorter than P25 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2015
CompletedFirst Submitted
Initial submission to the registry
March 16, 2015
CompletedFirst Posted
Study publicly available on registry
March 20, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2016
CompletedResults Posted
Study results publicly available
January 5, 2017
CompletedJanuary 5, 2017
November 1, 2016
1.5 years
March 16, 2015
November 8, 2016
November 8, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of Overall Survival (OS) in Study Patients
The efficacy of 3D MRSI-guided, dose escalated radiation in newly diagnosed glioblastoma (GBM) patients as measured by overall survival (OS). Overall survival (OS) is defined as the time elapsed from the start of study treatment until death. Surviving patients (including patients lost to follow up) will be censored at the date of last contact.
Up to 2 years
Secondary Outcomes (4)
Rate of Progression-Free Survival (PFS) in Study Patients
Up to 2 years
Rate of Grade 3 or Higher Toxicity as a a Consequence of Study Therapy.
2 years
Change in Quality of Life From Baseline in Study Participants
Up to 2 years
Patterns of Failure in Study Participants Post-Protocol Therapy
Up to 2 years
Study Arms (2)
Group 1: SIB + IMRT
EXPERIMENTAL* Simultaneous Integrated Boost (SIB) plus Fractionated Intensity Modulated Radiation therapy (IMRT), with concurrent Temozolomide therapy for 6 weeks; * 3D MRSI during week 3, end of RT and other protocol-defined time points during adjuvant Temozolomide therapy; * Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire administered at protocol-defined time points; * Adjuvant Temozolomide Therapy for up to 12 cycles.
Group 2: SRS Boost + IMRT
EXPERIMENTALFor patients with High-Risk Tumor Volumes (HTV) \<= 4cm; or multiple HTVs \<= 3 cm: * Stereotactic Radiosurgery Boost (SRS Boost) followed one week later by Fractionated Intensity Modulated Radiation therapy (IMRT), and concurrent Temozolomide therapy for 6 weeks; * 3D MRSI during week 3, end of RT and other protocol-defined time points during adjuvant Temozolomide therapy; * Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire administered at protocol-defined time points; * Adjuvant Temozolomide Therapy for up to 12 cycles.
Interventions
IMRT treatment will consist of 60 Gy in 30 fractions to PTV 60
Concurrently during radiation therapy. Adjuvant therapy administered daily on days 1 - 5 for 12 cycles. One cycle = 28 days: * Concurrent during Radiation Therapy: 75 mg/m\^2 orally for 6 weeks; * Post-radiation, adjuvant therapy: 150 mg/m\^2 - 200 mg/m\^2 orally daily on days 1 - 5 of each cycle.
FACT-Br Quality of Life (QOL) questionnaire to be completed by study patients as protocol specific timepoints
Patients will undergo SRS boost in a single fraction dose prior to IMRT treatment: HTV Maximum dimension vs. Prescribed Dose to HTV: ≤ 20 mm = 21 Gy; 21 mm - 30 mm = 18 Gy; 31 mm - 40 mm = 15 Gy.
Treatment shall consist of 60 Gy in 30 fractions to planning target volume (PTV) 60 and 75 Gy in 30 fractions to PTV 75.
Three Dimensional Magnetic Resonance Spectroscopy Imaging (MRSI) during pre-treatment, week 3 during radiation therapy, end of radiation therapy; will include standard gadolinium enhanced MRI prior to cycle 1, 5, 9, and post cycle 12 of adjuvant temozolomide therapy, per protocol.
Eligibility Criteria
You may qualify if:
- Histologically proven diagnosis of glioblastoma (WHO grade IV). Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.
- The tumor must have a supratentorial component
- Patients must have recovered from the effects of surgery, postoperative infection and other complications
- Karnofsky performance status \> 70
- Age \> 18 years
- Adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) \>/= 1500 cells/mm\^3
- Platelet count \> 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.)
- Patients on full-dose anticoagulants (e.g., warfarin or low-molecular weight (LMW) heparin) must meet both of the following criteria:
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- In-range international normalized ratio (INR) (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
- Adequate renal function, defined as follows:
- Blood urea nitrogen (BUN) \< 30 mg/dL
- Serum creatinine \< 1.5 x upper limit of normal (ULN)
- +8 more criteria
You may not qualify if:
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity or cervix are all permissible)
- Recurrent malignant glioma or evidence of leptomeningeal spread
- Metastases detected below the tentorium or beyond the cranial vault
- Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment
- Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation therapy fields
- Prior radiation therapy or chemotherapy for glioblastoma
- Severe, active co-morbidity, defined as follows:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the last 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- Severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
- Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
- Active (acute or chronic) or uncontrolled severe infections requiring intravenous antibiotics
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition or known HIV seropositivity. Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with HIV/AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- 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
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Miami
Miami, Florida, 33136, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Data were not analyzed due to insufficient number of evaluable subjects. Only one subject enrolled who was later withdrawn by the Investigator prior to assignment to any treatment group or receiving any protocol therapy.
Results Point of Contact
- Title
- Fazilat Ishkanian MD, PhD
- Organization
- University of Miami
Study Officials
- PRINCIPAL INVESTIGATOR
Fazilat Ishkanian, MD, PhD
University of Miami
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2015
First Posted
March 20, 2015
Study Start
March 1, 2015
Primary Completion
September 1, 2016
Study Completion
September 1, 2016
Last Updated
January 5, 2017
Results First Posted
January 5, 2017
Record last verified: 2016-11