Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage NSCLC (HAMLET)

Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage Non-small Cell Lung Cancer HAMLET Study

Rationale: An anatomical surgical resection is considered to be the standard of care in fit patients who present with early stage non-small cell lung cancer (NSCLC). However, surgery is less frequently performed in both elderly patients (aged ≥75 years), who represent the fastest-growing group of patients with stage I/II NSCLC, and in patients who have significant co-morbidity. Following the introduction of stereotactic ablative radiotherapy (SABR), an outpatient treatment that is typically delivered in between 3-8 fractions, the median survival of all elderly patients undergoing radiotherapy in The Netherlands increased by 9.3 months. Randomized trials comparing SABR and surgery have yet to be completed and results of the ongoing ACOSOG Z4032 studies will not be available in the within 5 years. A recent data retrospective study comparing both modalities has raised interesting questions about the impact of local therapy on recurrence patterns. It was found that a better loco-regional disease control rate was achieved with SABR.

Objective: To study the effect of surgery and SABR on both immunostimulatory (with primary endpoint CD8 positive cells) and immunosuppressive cells in peripheral blood in patients with early stage non-small cell lung cancer who are treated with either modality.

Study population: 40 patients with cT1-2aN0M0 either cytologically or histologically proven NSCLC.

Main study parameters/endpoints: To determine whether an increase in CD8 activity can be established after SABR in patients with early stage lung cancer and to compare this increase with that in patients undergoing a surgical intervention. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Only risks in participation are the risks with drawing blood. Subjects will not have any benefits. This pilot study will be used to generate information concerning both treatments useful for the decision to plan a future study in a larger series of patients.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Procedure: Surgery; Radiation: SABR

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VU Medical Center
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek Hospital
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GD
      • Erasmus MC Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cytologically or histologically proven cT1-2aN0M0 NSCLC
• Patients ≥ 18 years old
• Patients should be fit to undergo both treatments in accordance with institutional protocols

Exclusion Criteria:

• Patients with any signs of any co-existing infectious disease or immunosuppressive treatment (inhalation steroids are permitted)
• Mentally incapacitated subjects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgery; An anatomical surgical resection of primary tumor	Procedure: Surgery
Active Comparator: Radiotherapy; Stereotactic Ablative Radiotherapy (SABR), outpatient treatment that is typically delivered in between 3-8 fractions	Radiation: SABR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of IFN-gamma/ Granzyme B producing CD8 T cells	Number and activation status of peripheral CD8+ T cells	Baseline (week 0)
Number of IFN-gamma/ Granzyme B producing CD8 T cells	Number and activation status of peripheral CD8+ T cells	Week 1
Number of IFN-gamma/ Granzyme B producing CD8 T cells	Number and activation status of peripheral CD8+ T cells	Week 2
Number of IFN-gamma/ Granzyme B producing CD8 T cells	Number and activation status of peripheral CD8+ T cells	Week 3
Number of IFN-gamma/ Granzyme B producing CD8 T cells	Number and activation status of peripheral CD8+ T cells	Week 6

Secondary Outcome Measures

Outcome Measure	Time Frame
CD4/CD8 ratio in peripheral blood	Baseline
CD4/CD8 ratio in peripheral blood	Week 1
CD4/CD8 ratio in peripheral blood	Week 2
CD4/CD8 ratio in peripheral blood	Week 3
CD4/CD8 ratio in peripheral blood	Week 6
number of regulatory T cells	Baseline
number of regulatory T cells	Week 1
number of regulatory T cells	Week 2
number of regulatory T cells	Week 3
number of regulatory T cells	Week 6
Activation marker expression on T cells	Baseline
Activation marker expression on T cells	Week 1
Activation marker expression on T cells	Week 2
Activation marker expression on T cells	Week 3
Activation marker expression on T cells	Week 6

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Publications and helpful links

General Publications

• de Goeje PL, Smit EF, Waasdorp C, Schram MTB, Kaijen-Lambers MEH, Bezemer K, de Mol M, Hartemink KJ, Nuyttens JJME, Maat APWM, Hegmans JPJJ, Hendriks RW, Senan S, Aerts JGJV. Stereotactic Ablative Radiotherapy Induces Peripheral T-Cell Activation in Patients with Early-Stage Lung Cancer. Am J Respir Crit Care Med. 2017 Nov 1;196(9):1224-1227. doi: 10.1164/rccm.201610-2178LE. No abstract available.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 5, 2022
• Study Completion (Actual): April 5, 2022

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimated): July 2, 2015

Study Record Updates

• Last Update Posted (Actual): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: early stage; T cell activation; immune monitoring
• 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: NL42081.078.12