Clinical trial NCT04574856: Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma
Official title: A Phase II Study of Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2020-10-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will investigate whether or not intensified radiation therapy adapted during the radiation treatment course to high-risk, treatment-resistant tumor regions will improve overall survival in patients with newly diagnosed glioblastoma (GBM) compared to conventional chemoradiotherapy.


Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
* Karnofsky performance status \>=70
* Minimal life expectancy of 12 weeks
* Adequate bone marrow reserve (Hemoglobin ≥ 10 g/dL, absolute neutrophils ≥ 1500/mm3, platelet count ≥ 100,000/mm3), acceptable liver function (total bilirubin ≤ 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome), and ALT/AST ≤ 5 x ULN) and renal function (serum creatinine ≤ 2.0 mg/dL) within 14 day prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
* Maximal contiguous diameter of tumor based on high b-value diffusion MRI and DCE perfusion MRI ≤5 cm
* Patients must be registered within 6 weeks of most recent resection
* Females of child-bearing potential must have a negative pregnancy test within 14 days prior to registration. Patients with reproductive potential must agree to use an effective contraceptive method during treatment and study participation.

Exclusion Criteria:

* Recurrent glioma, or tumor involving the brainstem or cerebellum
* Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is \>3 years.
* Evidence of CSF dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination)
* Evidence of severe concurrent disease requiring treatment
* Prior invasive malignancy (except non-melanoma skin cancer or non-life limiting invasive malignancy that may not require treatment, such as low-risk prostate cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of breast, oral cavity or cervix are all permissible)
* Patients unable to undergo MRI exams (i.e. patients with non-compatible devices such as cardiac pacemakers, other implanted electronic devices, metallic prostheses, or ferromagnetic prostheses \[e.g. pins in artificial joints and surgical pins/clips\], or unable to receive gadolinium for MRI, as per the standard Department of Radiology MRI screening criteria)
* Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap as determined by treating physician
* Multifocal disease (\>1 lobe of involvement) of discontiguous contrast enhancing disease as seen on conventional MRI
* Pregnancy or lactation

Primary outcomes:
measure: 12-month overall survival rate
timeFrame: 12 months post radiation therapy (RT)
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Progression-free survival rate
timeFrame: 2 years
measure: Proportion of failures classified by relation to the high-dose radiation region
timeFrame: 2 years
measure: Advanced MRI Gross tumor volume (GTV) and its association with overall survival
timeFrame: 3 months post-RT
measure: Patient-reported quality of life (QOL) using EORTC QLQ-C30 and BN20
timeFrame: Up to 12 months post-RT
measure: Patient-reported symptom burden using MDASI-BT
timeFrame: Up to 12 months post-RT
measure: Patient objective neurocognitive function
timeFrame: Up to 12 months post-RT
measure: Grade 3 or higher treatment-related toxicities
timeFrame: 12 months post-RT
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: Michelle Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: