Clinical Trial - NCT03180502

Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma

Recruiting

Sponsor: NRG Oncology

Collaborators: National Cancer Institute (NCI)

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03180502

Protocol Info

Short Description: Randomize Phase II of Proton Vs.Photon Therapy (IMRT) for IDH Mutant, Low to Intermediate Grade Gliomas
Long Description: A Phase II Randomized Trial of Proton Vs. Photon Therapy (IMRT) for Cognitive Preservation in Patients With IDH Mutant, Low to Intermediate Grade Gliomas
MGH Status: Open
Sponsor: NRG Oncology
Disease Program: Proton

Next Steps


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Purpose

This randomized phase II clinical trial studies the side effects and how well proton beam or intensity-modulated radiation therapy works in preserving brain function in patients with IDH mutant grade II or III glioma. Proton beam radiation therapy uses tiny charged particles to deliver radiation directly to the tumor and may cause less damage to normal tissue. Intensity-modulated or photon beam radiation therapy uses high-energy x-ray beams shaped to treat the tumor and may also cause less damage to normal tissue. Patients will be more likely to be randomized to proton beam radiation therapy. It is not yet known if proton beam radiation therapy is more effective than photon-based beam intensity-modulated radiation therapy in treating patients with glioma.
Condition Title Intervention Phase
1p/19q Co-deletion Anaplastic Astrocytoma Diffuse Astrocytoma Glioma IDH1 Gene Mutation IDH2 Gene Mutation Oligoastrocytoma Oligodendroglioma WHO Grade III Glioma IMRT (Intensity-Modulated Radiation Therapy) Proton Beam Radiation Therapy Temozolomide Phase 2
Study Type Interventional
Official Title A Phase II Randomized Trial of Proton Vs. Photon Therapy (IMRT) for Cognitive Preservation in Patients With IDH Mutant, Low to Intermediate Grade Gliomas

Primary Outcome Measures

Change in cognition as measured by the CTB COMP score [Time Frame: Baseline to up to 10 years] [Designated as safety issue: ]


Secondary Outcome Measures

Change in quality of life as measured by the LASA scale [Time Frame: Up to 10 years] [Designated as safety issue: ]

Change in symptoms as measured by MDASI-BT [Time Frame: Baseline to up to 10 years] [Designated as safety issue: ]

Cognition as measured by COWA [Time Frame: Up to 10 years] [Designated as safety issue: ]

Cognition as measured by TMT parts A and B [Time Frame: Up to 10 years] [Designated as safety issue: ]

Cognition as measured by HVLT-R [Time Frame: Up to 10 years] [Designated as safety issue: ]

Incidence of adverse events (AEs) graded according to the National Cancer Institute's Common Terminology for Adverse Events version 4.0 [Time Frame: Up to 10 years] [Designated as safety issue: ]

Local control as assessed by RANO criteria [Time Frame: Up to 10 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: From randomization to the date of death, assessed up to 10 years] [Designated as safety issue: ]

Progression-free survival (PFS) [Time Frame: From date of randomization to date of progression or death, whichever occurs first, assessed up to 10 years] [Designated as safety issue: ]

Estimated Enrollment: 120
Study Start Date: August 2017
Estimated Study Completion Date: January 2030
Estimated Primary Completion Date: January 2025
Arms Assigned Interventions

Active Comparator:Arm I (photon-based IMRT, temozolomide)

Patients undergo photon-based IMRT QD, 5 days a week for 6 weeks for a total of 30 fractions. Beginning 4 weeks after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity.
Drug:Temozolomide
Chemotherapy drug

Experimental:Arm II (proton beam radiation therapy, temozolomide)

Patients undergo proton beam radiation therapy QD, 5 days a week for 6 weeks for a total of 30 fractions. Beginning 4 weeks after completion of radiation therapy, patients receive standard of care temozolomide for 5 days. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression of unacceptable toxicity.
Radiation:Proton Beam Radiation Therapy
Undergo proton beam radiation therapy

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Prior to STEP 1 REGISTRATION
  • Tumor tissue must be available for submission for central pathology review
  • Documentation from the enrolling site confirming the presence of IDH mutation and 1p/19q status; the provided information must document assays performed in clinical laboratory improvement amendments (CLIA)-approved laboratories
  • Only English speaking patients are eligible to participate as the cognitive and quality of life assessments are available only in English
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Karnofsky performance status of >= 70 within 30 days prior to registration
  • Absolute neutrophil count (ANC) >= 1,500 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
  • BUN < 30 mg/dl
  • Serum creatinine < 1.5 mg/dl
  • Post-operative magnetic resonance (MR) imaging with contrast is mandatory obtained for radiation therapy planning; enrolling sites are highly encouraged to obtain thin-slice (<1.5 mm) 3D T1 pre and post contrast and Axial T2/FLAIR sequences for planning purposes
  • Prior to STEP 2 REGISTRATION
  • The following baseline neurocognitive assessments must be completed and uploaded prior to step 2 registration: HVLT-R, TMT Parts A and B, and COWA
  • Completion of all items on the following baseline quality of life forms: MDASI-BT, LASA QOL, WPAI-GH and Employment Questionnaire. These quality of life forms will be required and data entered at step 2 registration.
  • Financial clearance for proton therapy treatment prior to step 2 registration
  • Centrally reviewed histologically proven diagnosis of supratentorial, Word Health Organization (WHO) grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma, with IDH mutation

Exclusion Criteria:

  • Definitive clinical or radiologic evidence of metastatic disease; if applicable
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity or cervix are permissible)
  • Prior cranial radiotherapy or radiotherapy to the head and neck where potential field overlaps would exist
  • Prior chemotherapy or radiotherapy for any brain tumor
  • Histologic diagnosis of glioblastoma (WHO grade IV) or pilocytic astrocytoma (WHO grade I)
  • Definitive evidence of multifocal disease
  • Planned use of cytotoxic chemotherapy during radiation (only adjuvant temozolomide therapy will be used on this protocol)
  • Patients with infra-tentorial tumors are not eligible
  • Prior history of neurologic or psychiatric disease believed to impact cognitive function
  • The use of memantine during or following radiation is NOT allowed
  • Severe, active co-morbidity defined as follows:
  • Unstable angina or congestive heart failure requiring hospitalization within 6 months prior to enrollment
  • 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 28 days prior to step 2 registration (Note: EKG to be performed only if clinical suspicion of cardiac issue)
  • New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to step 2 registration
  • Serious and inadequately controlled arrhythmia at step 2 registration
  • Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for surgical resection
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration
  • Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol
  • 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 (i.e., on dialysis or dialysis has been recommended)
  • Any other major medical illnesses or psychiatric treatments that in the investigator's opinion will prevent administration or completion of protocol therapy
  • Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction); note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03180502

Locations

  • United States, Florida
    • Miami Cancer Institute Miami, Florida, United States, 33176
  • United States, Illinois
    • Northwestern Medicine Cancer Center Delnor Geneva, Illinois, United States, 60134
    • Northwestern Medicine Cancer Center Warrenville Warrenville, Illinois, United States, 60555
  • United States, Maine
    • Maine Medical Center- Scarborough Campus Scarborough, Maine, United States, 04074
  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, Missouri
    • Washington University School of Medicine Saint Louis, Missouri, United States, 63110
  • United States, Texas
    • M D Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Washington
    • Seattle Cancer Care Alliance at Northwest Hospital Seattle, Washington, United States, 98133
    • University of Washington Medical Center Seattle, Washington, United States, 98195

Sponsors and Collaborators

NRG Oncology

National Cancer Institute (NCI)

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03180502
Other Study ID Numbers: NCI-2017-00203
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Glioma

Astrocytoma

Oligodendroglioma

Temozolomide

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019