Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01478854
First received: November 3, 2011
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.


Condition Intervention
Glioblastoma Multiforme
Radiation: Radiation
Drug: Chemotherapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • NPC Sparing [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To estimate the local recurrence (LR) rate at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM).


Secondary Outcome Measures:
  • radiation dose sparing assessment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with newly diagnosed GBM

  • Number of Participants with Cognitive Adverse Events [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To assess feasibility of evaluating cognitive function prospectively in patients undergoing NPC sparing RT for newly diagnosed GBM.

  • Oral assessments after treatment [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To explore if the potential change from baseline to six months in neurocognitive function as measured by the Mini Mental State Exam, Trail Making Test, Controlled Oral Word Association test (COWAT), Hopkins Verbal Learning Test-Revised, Digit Symbol Substitution Test is related to radiation dose to the NPC containing regions in patients treated with NPC sparing radiation for newly diagnosed GBM.


Estimated Enrollment: 30
Study Start Date: May 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neural Progeniter Cell Sparing Radiation with Temozolomide
All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy
Radiation: Radiation
Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI.
Drug: Chemotherapy
Temozolomide

Detailed Description:

Radiation therapy (RT) is an integral component of the management of brain tumors, but cognitive deficits following cranial irradiation are well documented. There is an association between damage to neural progenitor cells (NPC) and neurocognitive dysfunction. NPC are similarly known to play an important role in recovery from damage to the brain, including radiation-induced damage. However NPC are extremely sensitive to radiation. In spite of this information, current RT planning techniques do not limit the radiation dose to the NPC containing regions. Recent human studies have demonstrated that it is possible to use intensity modulated radiation therapy to reduce the radiation dose to NPC containing regions during RT for brain tumors, without compromising coverage of the tumor. We hypothesize that NPC-sparing RT will reduce neurocognitive decline following treatment for brain tumors, without compromising tumor local control. However, there is conflicting data regarding the role of NPC in the development of glioblastoma multiforme (GBM). Some studies suggest that GBM are derived from NPC whereas others have associated NPC with improved tumor control following therapy for GBM. Prior to evaluation of neurocognitive outcomes with NPC-sparing RT, it is therefore imperative to evaluate whether NPC-sparing RT techniques lead to increased LR in the spared NPC containing niches of the brain.

The proposed study is designed to evaluate LR in the spared regions of the brain following NPC sparing RT in patients with newly diagnosed GBM. Our research will consist of 3 specific aims: 1) Determine the LR rate at 1 year in the spared NPC containing niches in patients treated with NPC sparing RT for GBM; 2) Quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with GBM; 3) Determine if it is feasible to evaluate cognitive function prospectively in patients undergoing NPC sparing RT for GBM.

The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have newly diagnosed Glioblastoma Multifomre (GBM).
  • Patient must have undergone surgical resection and must begin radiation within 12 weeks of this procedure.
  • Patients must not have received previous irradiation to the brain.
  • Patient must be at least 18 years of age
  • Karnofsky performance status of greater than 60%
  • Patient must receive temozolomide concurrent with and following radiation.
  • If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception for the duration of study participation and for up to 12 weeks following the study. Should a women become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.
  • Patient must have the ability to understand and the willingness to sign a written informed consent document.
  • All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

  • Patients may not be receiving any other agents to treat their GBM
  • No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 2 years.
  • Patients with any other uncontrolled illness will be excluded.
  • Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. This applies to any woman who has not experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Male subjects must also agree to use effective contraception for the same period as above.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01478854

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Kristin Redmond, M.D. The Johns Hopkins University School of Medicine
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01478854     History of Changes
Other Study ID Numbers: J-10100, NA_00042009
Study First Received: November 3, 2011
Last Updated: February 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014