This is a study involving patients with recurrence, metastasis, or new primary malignancies in the thorax requiring radiation and who have previously received radiotherapy to the thorax, where re-irradiation is expected to exceed the dose constraints used for de novo treatments. Currently, when this group of patients needs another set of radiotherapy, there is a dose limitation based on a percentage of the previous treatment's dose. However, this dose often limits the effectiveness of repeated treatment, with little scientific support for such. Therefore, this study aims to determine the maximally tolerated dose of reirradiation in the thorax, with dose escalation implemented by sequentially increasing the normal tissue recovery factors (i.e. repair factors) to the previously delivered dose. Using a recovery factor equation associated with a 35% or lower rate of grade 3-5 treatment-related toxicity occurring within 1 year of treatment, accrual will start at level 1 (recovery factor = 10% at 6 months + 0.75% per month thereafter). Patients will be assigned to recovery factors 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 3-5 toxicity of 35% or less.
The REPAIR trial aims to identify the magnitude of radiation recovery in the thorax and enable safe reirradiation dose escalation. The trial will provide critical information to support shared-decision making and ensure the risk-benefit trade-offs of reirradiation align with each patient's wishes. In addition, the data from this study will be informative in guiding subsequent studies on the use of reirradiation for other sites (such as the brain, abdomen, and pelvis) and to inform future re-irradiation trials. The objective of this phase I study is to determine the safety of dose escalation via recovery factors applied against previously delivered doses for patients receiving thoracic reirradiation. This study will use a time-to-event continual reassessment method (TITE-CRM). The study design is based on previous thoracic dose escalation trials. The primary endpoint of this study is the maximally tolerated dose (MTD) of thoracic reirradiation, implemented by sequentially increasing the normal tissue recovery factors applied to the previously delivered dose. The MTD is the recovery factor equation associated with a ≤ 35% rate of grade 3-5 pre-specified treatment-related toxicity occurring within 1 year of treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Patients will be assigned to treatment doses using the TITE-CRM model.
Maximally tolerated dose (MTD)
MTD of radiotherapy for thoracic tumors. The MTD is the dose of radiotherapy associated with a \<35% rate of grade 3-5 toxicity occurring within 1 year of treatment.
Time frame: occurring within 1 year of treatment
Time to progression
Progression of treated disease
Time frame: 1-5 years
Time to distant metastases
Time to distant metastases
Time frame: 1-5 years
Progression-Free Survival
Progression-Free Survival
Time frame: 1-5 years
Overall survival
Overall survival
Time frame: 1-5 years
Patient reported outcome
Functional Assessment of Cancer Therapy: Lung (FACT-L)
Time frame: Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
Quality of Life - EuroQol 5-dimension 5-level
EuroQol 5-dimension 5-level
Time frame: Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
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