Feasibility of Primer Shot Radiotherapy for Non-small Cell Lung Cancer - PRIMER
NCT Number: NCT06528743
Acronym: PRIMER
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Patients With NSCLC Stage 2-4
Interventions: RADIATION: RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases.
Sponsor: The Netherlands Cancer Institute
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 34
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2029-08-01

Summary:
Intro/rationale: Radiotherapy employs uniform, equally spaced weekday fractions that do not account for changes in tumor radiosensitivity. However, radiobiological characteristics evolve during the radiotherapy schedule as reoxygenation increases radiosensitivity. In tumor-response simulations and preclinical experiments, it was superior to prime the tumor with one radiotherapy fraction, followed by a treatment break permitting mitotic cell death and reoxygenation of tumor cells.

Objective: To determine the safety and feasibility of primer shot fractionation for NSCLC.

Study design: A prospective non-randomized feasibility trial to test the safety of primer shot fractionation in a 3+3 phase with increasing treatment breaks, followed by an expansion cohort.

Study population: Patients with NSCLC stage 2-4, referred for palliative radiotherapy of the primary tumor and possibly (lymph node) metastases. Patients are allowed to receive systemic treatments, except for VEGFR-inhibitors. The 3+3 phase is followed by an expansion phase of 22 patients.

Intervention: All treatments are 5x6 Gy to all targets. Patients receive an increasing primer shot treatment break. In the 3+3 phase, the break between the first and the second radiotherapy fraction is: 1, 2 and 3 weeks. The maximum tolerated break length will be used for the expansion cohort.

Main study parameters/endpoints: The main study endpoint is the ability of patients to finish the radiotherapy schedule as planned. Secondary endpoints are tumor response at the end of treatment and 3 months thereafter, and acute toxicity.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on simulations and preclinical data, primer shot treatment breaks increase tumor control. However, the increased overall treatment time could potentially increase the chance a patient drops out before the radiotherapy schedule is finished. Because of the gradually prolonged break, this risk is relatively small and acceptable for this population. Additionally, patients are asked to fill in PRO-CTCAE lung subset questionnaires at the start of treatment and during follow-up. They will also receive 1 additional CT with contrast at fraction 5.

Primary Outcome Measures: the ability of patients to finish the radiotherapy schedule, The study is powered to find a decrease of response from 99% to no less than 84.15% (relative decrease of 15%)., 5 weeks
Secondary Outcome Measures: treatment response of the irradiated lesions, at the end of treatment and after 3 months|treatment associated ≥ grade 2 non-hematologic toxicity according to the NCI Common Terminology Criteria of Adverse Events (CTCAE version 5.0) (from the first radiotherapy fraction until 6 months after radiotherapy), from the first radiotherapy fraction until 6 months after radiotherapy|Patient-reported outcome (PRO)-CTCAE, up to 1 year after radiation.