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Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Overall Recruitment Status: Active, enrollment completed
 
Official Title
Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma
 
Region Sponsors
California - Northern
NRG Oncology
 
Acronym KP IRB No.
CN-15-2273-C
 
Study Type Phase
Clinical Trial Phase II
 
Study Population Description
Adults with Adult Giant Cell Glioblastoma, Adult Glioblastoma, or Adult Gliosarcoma
 
Purpose
This randomized phase II trial studies how well dose-escalated photon intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy works compared with standard-dose radiation therapy when given with temozolomide in patients with newly diagnosed glioblastoma. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as temozolomide, may make tumor cells more sensitive to radiation therapy. It is not yet known whether dose-escalated photon IMRT or proton beam radiation therapy is more effective than standard-dose radiation therapy with temozolomide in treating glioblastoma.
 
Detailed Description
PRIMARY OBJECTIVES: I. To determine if dose-escalated and -intensified photon IMRT or proton beam therapy (using a dose-per-fraction escalation with simultaneous integrated boost) with concomitant and adjuvant temozolomide improves overall survival, as compared to standard-dose photon irradiation with concomitant and adjuvant temozolomide. SECONDARY OBJECTIVES: I. To indirectly compare dose-escalated and -intensified photon IMRT to dose-escalated and -intensified proton beam therapy in terms of overall survival. II. To indirectly compare and record toxicities of dose-escalated and -intensified photon IMRT versus dose-escalated and -intensified proton beam therapy and directly compare the toxicities of these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide. III. To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves perceived cognitive symptom severity, as compared to dose-escalated and -intensified photon IMRT, and to directly compare symptom burden with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide. IV. To indirectly determine if dose-escalated and -intensified proton beam therapy with concomitant and adjuvant temozolomide improves neurocognitive function, as compared to dose-escalated and -intensified photon IMRT, and to directly compare neurocognitive function with these approaches versus standard-dose photon irradiation on the backbone of concomitant and adjuvant temozolomide. TERTIARY OBJECTIVES: I. Tissue banking for future translational science projects that will be determined based on the state of the science at the time the primary endpoint is reported and will be submitted to National Cancer Institute (NCI) for review and approval. II. To prospectively compare cluster of differentiation (CD)4 lymphopenia between dose-escalated and intensified proton beam therapy, dose-escalated and -intensified photon IMRT, and standard-dose photon irradiation. III. To explore the most appropriate and clinically relevant technological parameters to ensure quality and effectiveness throughout radiation therapy processes, including imaging, simulation, patient immobilization, target and critical structure definition, treatment planning, image guidance and delivery. To establish feasibility and clinical relevancy of quality assurance guidelines. To evaluate efficacy of quality assurance tools. OUTLINE: Patients are assigned to 1 of 2 groups depending on enrolling institution. Within each group, patients will be randomized 1:2 in favor of the experimental arms. GROUP I (PHOTON IMRT CENTERS): Patients are randomized to 1 of 2 treatment arms. ARM A1: Patients undergo standard-dose photon irradiation using 3-dimensional conformal radiation therapy (3D-CRT) or IMRT once daily (QD), 5 days a week for 23 fractions plus a boost of 7 additional fractions. ARM B: Patients undergo dose-escalated and -intensified photon IMRT QD, 5 days a week for a total of 30 fractions. GROUP II (PROTON CENTERS): Patients are randomized to 1 of 2 treatment arms. ARM A2: Patients undergo standard-dose photon irradiation using 3D-CRT or IMRT as in Arm A1. ARM C: Patients undergo dose-escalated and -intensified proton beam radiation therapy QD, 5 days a week for a total of 30 fractions. In all treatment arms, patients receive temozolomide orally (PO) QD on days 1-49 of radiation therapy. Beginning 4 weeks later, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.
 
Gender Age Limit
Male & Female
 
Inclusion Criteria
  • A diagnostic contrast-enhanced magnetic resonance imaging (MRI) (no other scan type allowed) of the brain must be performed postoperatively within 72 hours of resection. The enhancing tumor must have a maximal diameter of 5 cm
  • The GBM tumor must be located in the supratentorial compartment only
  • Histologically proven diagnosis of glioblastoma (WHO grade IV) confirmed by central review prior to step 2 registration
  • Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient quantity for analysis of O6-methylguanin-DNA-methyltransferase (MGMT) status
  • Patients must have at least 1 block of tumor tissue. Submission of 2 blocks is strongly encouraged. At least 1 cubic centimeter of tissue composed primarily of tumor must be present
  • Diagnosis must be made by surgical excision, either partial or complete. Stereotactic biopsy or cavitron ultrasonic suction aspirator (CUSA) technique not allowed
  • The patient must have recovered from effects of surgery, postoperative infection, and other complications within 14 days prior to step 2 registration
  • Documentation of steroid doses
  • Karnofsky performance status >= 70
  • Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 10.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable)
  • Bilirubin =< 1.5 upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • CD4 lymphocyte count within 14 days prior to step 2 registration
  • Negative serum pregnancy test obtained within 14 days prior to step 2 registration
  • Please contact study team for more eligibility criteria
 
Exclusion Criteria
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for < 3 years
  • Recurrent or multifocal malignant gliomas
  • Any site of distant disease
  • Prior chemotherapy or radiosensitizers for cancers of the head and neck region (prior chemotherapy for a different cancer is allowable)
  • 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 fields
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use contraception
  • Patents treated on any other therapeutic clinical protocols within 30 days prior to step 2 registration
  • Inability to undergo MRI
  • Severe, active co-morbidity, defined as follows: Unstable angina at step 2 registration
  • Transmural myocardial infarction within the last 6 months prior to step 2 registration
  • Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days prior to step 2 registration
  • Serious and inadequately controlled arrhythmia at step 2 registration
  • Acquired immune deficiency syndrome (AIDS) based upon current CDC definition
  • Any other severe immunocompromised condition
  • 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
  • End-stage renal disease
  • Please contact study team for more eligibility criteria

 
Keywords and/or Specific Medical Conditions
  • Adult Glioblastoma
  • Molecular Mechanisms of Pharmacological Action
  • Adult Gliosarcoma
  • Neoplasms
  • Alkylating Agents
  • Neoplasms by Histologic Type
  • Antineoplastic Agents
  • Neoplasms, Germ Cell and Embryonal
  • Antineoplastic Agents, Alkylating
  • Neoplasms, Glandular and Epithelial
  • Astrocytoma
  • Neoplasms, Nerve Tissue
  • Dacarbazine
  • Neoplasms, Neuroepithelial
  • Glioblastoma
  • Neuroectodermal Tumors
  • Glioma
  • Temozolomide
  • Gliosarcoma
  • Adult Giant Cell Glioblastoma
 
KP Clinical Facility
  • Diablo Medical Center-Deer Valley
  • Diablo Medical Center-Walnut Creek
  • Fremont Medical Center
  • Fresno Medical Center
  • Hayward Medical Center
  • Oakland Medical Center
  • Redwood City Medical Center
  • Richmond Medical Center
  • Roseville Medical Center-Rancho Cordova
  • Sacramento Medical Center
  • San Francisco Medical Center
  • San Leandro Medical Center
  • Santa Clara Medical Center-Homestead
  • Santa Teresa Medical Center-San Jose
  • South Sacramento Medical Center
  • South San Francisco Medical Center
  • Vallejo Medical Center
  • Vallejo Medical Center-Vacaville
 
Clinical Area


Principal Investigator:
Louis Fehrenbacher, MD
Contact Information:
- Desiree Goldstein, RN
-Desiree.Goldstein@kp.org
-Vallejo Medical Center


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