Non-ablative Oligofractionated Radiation Therapy Before Surgical Transplantation As Radiovaccination

Official Title

Non-ablative Oligofractionated Radiation Therapy Before Surgical Transplantation As Radiovaccination

Summary:

This is a prospective phase I study to determine the safety and feasibility of non-ablative oligofractionated radiation therapy (NORT) before lung transplantation for patients with underlying pulmonary malignancy. We hypothesize that heterogeneous dose distributions could generate a vaccination effect against the tumour by creating anti-tumoural immune response in the body and these patients may be immunized against their tumour which could reduce the risk of cancer recurrence after transplantation despite the anti-rejection medications required for the transplantation.

Trial Description

Primary Outcome:

• Maximum Tolerated Dose for Radiation

Secondary Outcome:

• Patient Morbidity
• Local recurrence

This study is designed to deliver short courses of radiation to the pulmonary malignancy followed by resection of the radiated tumour at the time of transplant. The study is a 3+3 phase 1 study with incremental dose of radiation to determine the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) will be defined as grade 3+ radiation related toxicity. If one DLT is seen, then an additional 3 patients will be treated at the same dose level. If 2 or more DLT are seen at any given dose level, then the previous dose level will be defined as the MTD. A minimum of 3 patients and maximum of 18 patients will be included for the phase 1a. Due to the expected higher radiation risks in patients with end-stage ILD (group 1), these patients will be stratified separately from non-ILD patients (group 2, 3 and 4) during phase 1a. Dose tested are: 3 x 400 cGy, 3 x 600 cGy and 3 x 800 cGy for the ILD cohort and 3 x 800 cGy, 3 x 1000 cGy and 3 x 1200 cGy for the non-ILD cohort. Once the MTD is determined, patients will proceed to phase 1b using the MTD determined in the phase 1a. ILD and non-ILD patients may have different MTD so two separate phase Ib cohorts will be conducted. A total of 12 patients will be included for each cohort in the phase 1b. The dose distribution will be administered using a standard homogenous dose distribution for tumours ≤2 cm, and an heterogeneous dose distribution for tumours >2 cm.

View this trial on ClinicalTrials.gov