NCT06558175

Reirradiation Dose Escalation in Thoracic Cancers

A Safety and Efficacy Trial of Reirradiation Dose Escalation in Thoracic Cancers: Re-evaluating Previous Dose and Allowing Increasing Recovery (REPAIR)

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Thoracic Cancer
• Lung Cancer
• Esophageal Cancer

Interventions

Type	Name	Description
RADIATION	stereotactic body radiation therapy (SBRT)	Patients will be assigned to treatment doses using the TITE-CRM model.

Timeline

• Start date: 2024-10-30
• Primary completion: 2026-10-30
• Completion: 2027-01-29
• First posted: 2024-08-16
• Last updated: 2024-08-16