This multi-centre phase I dose-escalation study will use a time-to-event continual reassessment method (TIT-CRM). Accrual will start at level 1 (60 Gy in 8 fractions). Patients will be assigned to treatment doses using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3 toxicity of 30% or less.
This study will use a time-to-event continual reassessment method (TITE-CRM). The study design is based on RTOG 0813 (described above), but with a more cautious approach, since the patients herein may constitute a high-risk subset of the patients enrolled in RTOG 0813. The modifications include a starting dose (60 Gy in 8 fractions) herein that is lower than the safe dose for central tumors as determined by RTOG 0813 (60 Gy in 5 fractions), and longer follow-up period during which patients are considered at-risk for toxicity, (i.e. two years herein vs. one year in RTOG 0813). The primary endpoint of this study is the maximally tolerated dose (MTD) of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a \<30% rate of grade 3-5 toxicity occurring within 2 years of treatment. Local Progression, Regional nodal progression, Distant metastases, Progression-Free Survival, Overall survival, patient reported outcomes and quality of life. The correlative objectives of this study are to determine the prognostic value of ctDNA levels measured pre-treatment, at the end of treatment and 3- and 12-months after treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Patients will be assigned to treatment doses using the TITE-CRM model.
BC Cancer -Vancouver Island
Vancouver, British Columbia, Canada
London Regional Cancer Program
London, Ontario, Canada
Sunnybrook Odette Cancer Centre
Toronto, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Maximally tolerated dose (MTD)
MTD of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a \<30% rate of grade 3-5 toxicity occurring within 2 years of treatment.
Time frame: Occurring within 2 years of treatment
Time to Local Progression
Time frame: 3-5 years
Regional nodal progression
Defined as presence of enlarged lymph nodes \>1 cm \[short axis\] in the hilum or mediastinum.
Time frame: 3-5 years
Time to distant metastases
Time frame: 3-5 years
Progression-Free Survival
Time frame: 3-5 years
Overall survival
Time frame: 3-5 years
Patient reported outcome
FACT-L
Time frame: Before treatment & at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
Quality of Life
EQ-5D-5L
Time frame: Before treatment & at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
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Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, Canada
McGill University Health Centre-Cedars Cancer Centre
Montreal, Quebec, Canada
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada