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

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.

Study Overview

• Status: Recruiting
• Conditions: Patients With Non-small-cell Lung Cancer
• Intervention / Treatment: Radiation: RT (5x6 Gy) to the primary tumor and, if indicated, to lymph node and/or distant metastases.

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zeno Gouw; Phone Number: +31205129111; Email: z.gouw@nki.nl
• Study Contact Backup: Name: Evelien Schouten; Phone Number: +31205129111; Email: ev.schouten@nki.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
    • Contact: Zeno Gouw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Radiation: 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.
Experimental: 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	Radiation: 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.
Experimental: 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	Radiation: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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
Tumor response	the relative volume change after radiotherapy vs the CTRT.	at the end of treatment and after 3 months
Patient-reported outcome patient-reported outcome- Common Terminology Criteria of Adverse Events (PRO)-CTCAE		up to 1 year after radiation.

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: N23PSR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No