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Stem Cell Radiotherapy and Temozolomide for Newly Diagnosed High-grade Glioma (STRONG)

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ClinicalTrials.gov Identifier: NCT02039778
Recruitment Status : Terminated (Poor Accural)
First Posted : January 20, 2014
Results First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Collaborator:
St. Luke's-Roosevelt Hospital Center
Information provided by (Responsible Party):
Beth Israel Medical Center

Tracking Information
First Submitted Date  ICMJE January 16, 2014
First Posted Date  ICMJE January 20, 2014
Results First Submitted Date  ICMJE January 25, 2017
Results First Posted Date  ICMJE June 5, 2017
Last Update Posted Date June 5, 2017
Study Start Date  ICMJE December 2013
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2017)
  • Overall Survival [ Time Frame: 12 months ]
    The overall survival of patients with newly diagnosed high-grade glioma (HGG) treated with concurrent ScRT and temozolomide, followed by post-radiation temozolomide (and compare to historical controls).
  • Progression-free Survival [ Time Frame: 12 months ]
    The progression-free survival of patients with newly diagnosed HGG treated with concurrent ScRT and temozolomide, followed by post-radiation temozolomide (and compare to historical controls).
Original Primary Outcome Measures  ICMJE
 (submitted: January 16, 2014)
  • Overall Survival [ Time Frame: 12 months ]
    To estimate the overall survival of patients with newly diagnosed high-grade glioma (HGG) treated with concurrent ScRT and temozolomide, followed by post-radiation temozolomide (and compare to historical controls).
  • Progression-free Survival [ Time Frame: 12 months ]
    To estimate the progression-free survival of patients with newly diagnosed HGG treated with concurrent ScRT and temozolomide, followed by post-radiation temozolomide (and compare to historical controls).
Change History Complete list of historical versions of study NCT02039778 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2017)
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 36 months ]
    The short-and long-term toxicity of ScRT (and compare to historical controls).
  • Neurocognition [ Time Frame: 36 month ]
    The potential neurocognitive effects of ScRT by the Hopkins Verbal Learning Test (HVLT), Mini-mental status exam (MMSE), Trail Making Tests A/B (TMT), and Controlled Word Association Test (COWAT).
  • Quality of Life [ Time Frame: 36 months ]
    The impact of ScRT on health-related quality of life (HRQOL) as assessed by EORTC Quality of Life Questionnaire (EORTC QLQ-C30)/Brain Cancer Module (BCM 20), Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR), and Activities of Daily Living Scale (ADLS) during ScRT.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2014)
  • Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 36 months ]
    To determine the short-and long-term toxicity of ScRT (and compare to historical controls).
  • Neurocognition [ Time Frame: 36 month ]
    To determine the potential neurocognitive effects of ScRT by the Hopkins Verbal Learning Test (HVLT), Mini-mental status exam (MMSE), Trail Making Tests A/B (TMT), and Controlled Word Association Test (COWAT).
  • Quality of Life [ Time Frame: 36 months ]
    Determine the impact of ScRT on health-related quality of life (HRQOL) as assessed by EORTC Quality of Life Questionnaire (EORTC QLQ-C30)/Brain Cancer Module (BCM 20), Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR), and Activities of Daily Living Scale (ADLS) during ScRT.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stem Cell Radiotherapy and Temozolomide for Newly Diagnosed High-grade Glioma
Official Title  ICMJE STRONG Trial - Stem Cell Radiotherapy (ScRT) and Temozolomide for Newly Diagnosed High-grade Glioma (HGG): A Prospective, Phase I/II Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Malignant Glioma
  • Brain Tumors
  • Anaplastic Astrocytoma
Intervention  ICMJE Radiation: Stem Cell Radiotherapy (ScRT) and Temozolomide

Stem Cell Radiotherapy (ScRT) and Temozolomide:

The postoperative surgical bed + edema + margin & the ipsilateral subventricular zone (contoured as a 5mm rim of tissue around the ipsilateral lateral ventricles) will be included within the initial target volume and treated to 46 Gy in 23 fractions. After 46 Gy, the conedown or boost volume (surgical cavity + margin) will be treated to a total of 60 Gy, with seven additional fractions of 2 Gy each (14Gy boost dose).

Temozolomide will be administered continuously from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2. The drug will be administered orally on an empty stomach, the first dose to be given the night prior or morning of the first radiation fraction, and continued until the last radiation fraction is completed (including weekends and holidays).

Other Names:
  • Intensity Modulated Radiation Therapy (IMRT)
  • Temozolomide
  • Stem Cell Radiotherapy
Study Arms  ICMJE Experimental: Stem Cell Radiotherapy and Temozolomide

One treatment of 2.0 Gy will be given daily 5 days per week for a total of 60.0 Gy over 6 weeks.

Intensity Modulated Radiation Therapy (IMRT) Is Mandated; Proton therapy (Intensity-modulated proton therapy [IMPT] preferred) is an acceptable treatment modality.

Temozolomide will be administered continuously from day 1 of radiotherapy to the last day of radiation at a daily oral dose of 75 mg/m2. The drug will be administered orally on an empty stomach, the first dose to be given the night prior or morning of the first radiation fraction, and continued until the last radiation fraction is completed (including weekends and holidays).

Intervention: Radiation: Stem Cell Radiotherapy (ScRT) and Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 6, 2017)
4
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2014)
83
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02039778
Other Study ID Numbers  ICMJE 13-0151
13-0151 ( Other Identifier: 13-0151 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Beth Israel Medical Center
Study Sponsor  ICMJE Beth Israel Medical Center
Collaborators  ICMJE St. Luke's-Roosevelt Hospital Center
Investigators  ICMJE
Principal Investigator: Ilan Shapira, MD St. Luke's - Roosevelt Hospitals& Beth Israel Medical Center
Principal Investigator: Rahul Parikh, MD Roosevelt Hospital
PRS Account Beth Israel Medical Center
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP