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
Summary:
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 tumour cells
and shrink tumours. Specialized radiation therapy that delivers a high dose of radiation
directly to the tumour may kill more tumour cells and cause less damage to normal tissue.
Drugs, such as temozolomide, may make tumour 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.
Trial Description
Primary Outcome:
- Overall survival (OS) compared between dose-escalated and -intensified photon IMRT or proton beam therapy with concomitant and adjuvant temozolomide and the standard-dose photon irradiation with concomitant and adjuvant temozolomide
Secondary Outcome:
- OS when compared between dose-escalated and -intensified photon IMRT to dose-escalated and -intensified proton beam therapy
- Progression-free survival (PFS)
- Incidence of treatment-related toxicity, as measured by the Common Terminology Criteria for Adverse Events version 4
- Change in perceived cognitive function, as measured by M.D. Anderson Symptom Inventory Brain Tumour
- Change in neurocognitive function, as measured by Hopkins' Verbal Learning Test-Revised, Trail Making Test Parts A and B, and Controlled Oral Word Association Test
- Change in CD4 lymphopenia count
- Use of magnetic resonance diffusion and perfusion imaging to differentiate between tumour progression and pseudo-progression
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.
View this trial on ClinicalTrials.gov
