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 OBJECTIVES:
- 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:
- To indirectly compare
dose-escalated and -intensified photon IMRT to dose-escalated and
-intensified proton beam therapy in terms of overall survival.
- 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.
- 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 perceived
cognitive symptom severity, as compared to standard-dose photon
irradiation with concomitant and adjuvant temozolomide.
- 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
neurocognitive function, as compared to standard-dose photon irradiation
with concomitant and adjuvant temozolomide.
- 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.
- 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:
- 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.
- To prospectively
compare CD4 lymphopenia between dose-escalated and intensified proton
beam therapy, dose-escalated and -intensified photon IMRT, and
standard-dose photon irradiation and determine whether CD4 lymphopenia
impacts overall survival.
- 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.
- To explore the most appropriate and clinically relevant advanced and standard MRI imaging parameters.
- To evaluate the feasibility of
differentiating pseudo-progression and true progression in a multi
institutional setting using MR diffusion and perfusion imaging.
- To evaluate for early, imaging biomarkers of response and overall survival.
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 cycles 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
