Clinical trial NCT02039778: Stem Cell Radiotherapy and Temozolomide for Newly Diagnosed High-grade Glioma
Official title: STRONG Trial - Stem Cell Radiotherapy (ScRT) and Temozolomide for Newly Diagnosed High-grade Glioma (HGG): A Prospective, Phase I/II Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Glioblastoma
Malignant Glioma
Brain Tumors
Anaplastic Astrocytoma
Keywords: Glioblastoma
High-grade Glioma
Brain Tums
Temozolomide
Stem cell radiation therapy
IMRT
Proton beam radiotherapy
Conventional external beam radiotherapy
Quality of Life
Neurocognition
Lead sponsor: Beth Israel Medical Center
Sponsor class: OTHER
Collaborators: name: St. Luke's-Roosevelt Hospital Center
First posted: 2014-01-20
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: There are preliminary studies that suggest that radiation therapy to areas of the brain containing cancer stem cells (in addition to the area where the tumor was surgically treated) may help patients with high-grade brain tumors live longer. The purpose of this study is to determine whether the addition of stem-cell radiation therapy to the standard chemoradiation will further improve the outcome. The investigators will collect information about the patient's clinical status, disease control, neurocognitive effects, and quality of life during follow-up in our department.

The purpose of the study is to improve the overall survival patients with newly diagnosed malignant brain tumors treated with stem cell radiation therapy and chemotherapy. The investigators will also measure how patients treated with this novel method of radiation therapy do over time in terms of disease control, potential neurocognitive side effects, overall function, and quality of life.

Detailed description: Even after optimal standard treatment, the outcome for patients suffering from glioblastoma (GB) is currently dismal, and temozolomide adds a modest survival benefit at high monetary cost and is accompanied by considerable toxicity. A possible explanation for the failure of radiotherapy to cure GB is the observation that glioma cells migrate widely into healthy bilateral brain tissue from one or more foci of origin. These isolated cells are not detected by current radiological techniques or even imaging and therefore usually not included into the target volume during radiotherapy. In this present study the investigators would like to test the hypothesis that the dose prescribed to the normal tissue stem cell niche in the adult brain will influence the effectiveness of radiotherapy for patients suffering from HGG/GB as these niches may serve as a harbor for radioresistant glioma stem cells, which are the only cells in a HGG believed to able to repopulate a tumor.

The hypothesis is based on previous reports showing that adult normal tissue stem cells reside in the lateral periventricular regions of the lateral ventricles and animal studies reporting that transformation of normal tissues stem cells but not differentiated cells lead to tumor formation. This unique anatomical pattern of the brain that clearly separates stem cell niches as a potential pool of cancer stem cell (CSC's) from differentiated tissue make this an ideal model system to study the impact of radiation dose given to these stem cell niches. Therefore, prospective, randomized clinical trials are needed to address the efficacy and toxicity of including the CSC-containing subventricular region as additional target volumes into treatment plans for patients suffering from HGG/GB. This intervention could dramatically improve the outcomes of patients suffering from progressive, relapsing disease despite our best efforts currently.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed with high grade glioma (grade 3 or 4) having completed surgery.
* Patients must be ≥ 18 and ≤ 70 years of age;
* WHO/ECOG Performance Status of 2 or less.
* MRI of the brain as delineated above.
* Patients must sign a study-specific informed consent prior to study entry.

Exclusion Criteria:

* Evidence of brainstem involvement on radiographs;
* Evidence of oligodendroglioma histology.
* Evidence of progressive disease at the time of study entry;
* Evidence of extracranial distant metastatic disease;
* Prior cranial irradiation;
* Patients may not be entered on other studies that have progression free, disease free, or overall survival as a primary endpoint;
* Patients with synchronous or prior malignancy, other than non-melanomatous skin cancer unless disease free greater than 3 years;
* Pregnant women are ineligible as treatment involves unforeseeable risks to the participant and to the embryo or fetus; patients with childbearing potential must practice appropriate contraception.

Primary outcomes:
measure: Overall Survival
timeFrame: 12 months
measure: Progression-free Survival
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 36 months
measure: Neurocognition
timeFrame: 36 month
measure: Quality of Life
timeFrame: 36 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Roosevelt Hospital
state: New York
Study officials:
affiliation: St. Luke's - Roosevelt Hospitals& Beth Israel Medical Center
name: Ilan Shapira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Roosevelt Hospital
name: Rahul Parikh, MD
role: PRINCIPAL_INVESTIGATOR
References: