Feasibility of Primer Shot Radiotherapy for Non-small Cell Lung Cancer - PRIMER

NCT ID: NCT06528743

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-08
• Study Completion Date: 2029-08-01

Brief 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.

Conditions

Patients With Non-small-cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Primer shot treatment break of 1 week

Patients receive an increasing primer shot treatment break. In arm 1, the break between the first and the second radiotherapy fraction is 1 week

Group Type: EXPERIMENTAL

RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases.

Intervention Type: RADIATION

Patients will receive RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases. Enrolled patients will receive a fractionation scheme with increasing break length.

Primer shot treatment break of 2 weeks

Patients receive an increasing primer shot treatment break. In arm 1, the break between the first and the second radiotherapy fraction is 2 weeks

Group Type: EXPERIMENTAL

RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases.

Intervention Type: RADIATION

Patients will receive RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases. Enrolled patients will receive a fractionation scheme with increasing break length.

Primer shot treatment break of 3 weeks

Patients receive an increasing primer shot treatment break. In arm 1, the break between the first and the second radiotherapy fraction is 3 weeks

Group Type: EXPERIMENTAL

RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases.

Intervention Type: RADIATION

Patients will receive RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases. Enrolled patients will receive a fractionation scheme with increasing break length.

Interventions

RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases.

Patients will receive RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases. Enrolled patients will receive a fractionation scheme with increasing break length.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• NSCLC (either pathology proven or sufficient clinical suspicion to be treated as NSCLC), referred for palliative radiotherapy of at least the primary tumor site.
• Stage 2-4
• WHO performance score 0-2.
• Provision of signed, written and dated IC prior to any study specific procedures.

Exclusion Criteria

• Interstitial lung disease
• Treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors
• Prior thoracic radiotherapy (>20 Gy EQD2 a/b 3) overlapping with the current planning target volume

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Zeno Gouw

Role: CONTACT

z.gouw@nki.nl

+31205129111

Evelien Schouten

Role: CONTACT

ev.schouten@nki.nl

+31205129111

Facility Contacts

Zeno Gouw

Role: primary

Other Identifiers

N23PSR

Identifier Type: -

Identifier Source: org_study_id