Clinical trial NCT02206230: Trial of Hypofractionated Radiation Therapy for Glioblastoma
Official title: A Randomized Controlled Trial of Conventional Versus Hypofractionated Radiation Therapy With Temozolomide for Patients With Newly Diagnosed Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Keywords: glioblastoma
radiotherapy
hypofractionated radiotherapy
Lead sponsor: AHS Cancer Control Alberta
Sponsor class: OTHER
Collaborators: name: Cross Cancer Institute
First posted: 2014-08-01
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1, randomized, open label
Primary purpose: TREATMENT

Brief summary: This study is being done to compare standard radiation therapy with hypofractionated radiation therapy for patients with newly diagnosed glioblastoma

Detailed description: Hypofractionated radiation therapy (RT) in the treatment of patients with glioblastoma, 18 - 70 years of age with good performance status (ECOG 0 - 2), will be well tolerated and yield survival non-inferior to conventional fractioned RT, allowing significant abbreviation of the length of the radiation course required for these patients with limited survival. The importance of hypofractionation is, therefore, not in improving survival, but rather to shorten RT duration to improve patient comfort and convenience. This approach is pertinent given the limited life expectancy of glioblastoma and has been used in patients with prolonged survival including breast and prostate cancers.

Eligibility criteria: Inclusion Criteria:

1. Newly-diagnosed, histologically proven, intracranial glioblastoma or gliosarcoma treated with maximal safe resection, which may be biopsy alone if resection is not possible.
2. History and physical examination, including neurological examination, within 14 days prior to randomization.
3. Age between 18 and 70 years, inclusive.
4. ECOG performance score 0-2.
5. Stable or decreasing dose of corticosteroids for at least 14 days prior to randomization (Stupp et al.).
6. Laboratory evaluation obtained within 7 days prior to randomization, with adequate function as defined below: (Stupp et al.)

   1. ANC ≥ 1.5 x 10\^9/L
   2. Platelets ≥ 100 x 10\^9/L
   3. Serum creatinine ≤ 1.5 times ULN
   4. Total serum bilirubin ≤ 1.5 times ULN
   5. ALT \< 3 times ULN
   6. AST \< 3 times ULN
   7. Alkaline phosphatase \< 3 times ULN
7. Patients must sign a study-specific informed consent prior to study registration and must be willing to comply with study treatment, questionnaire completion and follow-up.

Exclusion Criteria:

1. Recurrent or multifocal malignant gliomas. Multicentric gliomas, defined as multiple, discrete areas of enhancement on T1 weighted MRI sequences with contrast all contained within one connected region of abnormality on T2 weighted/FLAIR MRI sequences, are allowed to enroll on this study.
2. Prior invasive malignancy (except for non-melanomatous skin cancer) unless expected survival from prior malignancy is ≥ 5 years.
3. Prior head or neck RT (except for T1 glottic cancer), or systemic therapy precluding delivery of concurrent and adjuvant temozolomide
4. Treatment with any other therapeutic clinical protocol within 30 days prior to study registration or during participation in the study.
5. Severe, active co-morbidity, defined as follows:

   1. Unstable angina and/or congestive heart failure requiring hospitalization
   2. Transmural myocardial infarction within the last 6 months
   3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study registration
   4. Any severe, active co-morbidity precluding delivery of temozolomide.
6. Women of child-bearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
7. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to temozolomide.

Primary outcomes:
measure: Overall survival
timeFrame: Patients without an event will be censored the last time they were known to be alive. Median, 6-month, 1-year, and 2-year OS rates will be measured.
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Patients without an event will be censored at date of last follow-up for progression. Patients with no post-baseline follow-up for progression will be censored at day of randomization. Median, 6-month, 1-yr, and 2-yr PFS rates will be measured
measure: Adverse events according to NCI CTCAE version 4.0 criteria.
timeFrame: Evaluated weekly during radiation therapy; on C1D1 and at the end of every 2 cycles of adjuvant temozolomide; post-treatment follow-up every 4 months for 2 years, then every 6 months for years 3-5 up until progression/palliative
measure: Health-related quality-of-life as assessed by MMSE and EORTC QLQ-C30/QLQ-BN20 questionnaires.
timeFrame: Evaluated at baseline, weekly during radiation therapy, at the end of every 2 cycles of adjuvant temozolomide, and post-treatment follow-up every 4 months for 2 years, then every 6 months for years 3-5 up until progression/palliative
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
Study officials:
affiliation: Cross Cancer Institute
name: Samir Patel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yang F, Dinakaran D, Heikal AA, Yaghoobpour Tari S, Ghosh S, Amanie J, Murtha A, Rowe LS, Roa WH, Patel S. Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma. Radiother Oncol. 2022 Dec;177:152-157. doi: 10.1016/j.radonc.2022.10.016. Epub 2022 Oct 20.