MRSI Guided Dose Escalated Radiation in Glioblastoma

Glioblastoma Clinical Trial

Official title:

Phase II Study of Dose Escalated, Targeted Radiation Therapy Using 3D Magnetic Resonance Spectroscopy Imaging (MRSI) in Newly Diagnosed Glioblastoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02394665
• Other study ID #: 20140540
• Status: Terminated
• Phase: Phase 2
• First received: March 16, 2015
• Last updated: September 29, 2016
• Start date: March 2015

Study information

• Verified date: September 2016
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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/mm3

• Platelet count >/= 100,000 cells/mm3

• 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 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 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:

• BUN </= 30 mg/dL

• Serum creatinine </= 1.5 x ULN

• Adequate hepatic function, as defined below:

• Bilirubin </= 1.5 normal range

• ALT </= 3x normal range

• AST </= 3x normal range

• Patients must not be pregnant (positive pregnancy test) or breast feeding; pregnancy test must be done within 7 days prior to registration. Effective contraception (men and women) must be used in patients of child-bearing potential while on study treatment and for 6 months after.

• Ability to understand and the willingness to sign a written informed consent document

• Ability to have MRI Scans

• Ability to swallow capsules

Exclusion Criteria:

• 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 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 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

• Other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy

• Pregnancy

• Women who are breast feeding

• Prior allergic reaction to temozolomide

• Treatment on any other therapeutic clinical protocol

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter their absorption of temozolomide (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

• Contraindications to MRI including but not limited to, pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steelworker or other implants

• Need to continue treatment with any prohibited medication (e.g. antioxidants) or have not completed the appropriate washout period.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Radiation:
• Intensity Modulated Radiation Therapy
IMRT treatment will consist of 60 Gy in 30 fractions to PTV60.

Drug:
• Temozolomide
Concurrent with six weeks of radiation therapy. After 28 day break then daily on days 1 - 5 of each cycle, for up to 12 cycles. One cycle = 28 days

Device:
• Three Dimensional Volumetric MRS Imaging
3D MRSI at week 3 of radiation therapy, and at the end of radiation therapy, and prior to cycle 1, 4, 7 and 10 of adjuvant (post-radiation) therapy

Behavioral:
• FACT-BR Questionnaire
FACT-BR Quality of Life (QOL) Questionnaire to be completed by study patients as protocol specific timepoints

Radiation:
• Stereotactic Radiosurgery Boost
Administered one week prior to fractionated radiation therapy
• Simultaneous Integrated Boost
Treatment shall consist of 60 Gy in 30 fractions to PTV60 and 75 Gy in 30 fractions to PTV75

Device:
• MRI
MRI w/ or w/Gadolinium at week 3 of radiation therapy, and at the end of radiation therapy, and prior to cycle 1, 4, 7 and 10 of adjuvant (post-radiation) therapy

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of overall survival (OS) in study patients	The efficacy of 3D MRSI guided, dose escalated radiation in newly diagnosed GBM patients as measured by overall survival (OS)	2 years	No
Secondary	Number of patients experiencing adverse events as a consequence of study therapy	To assess acute grade 3 or higher toxicity as a consequence of study therapy	2 years	Yes
Secondary	Rate of Progression-Free Survival (PFS) in study patients	To determine progression-free survival (PFS) in study patients	2 years	No