Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage NSCLC (HAMLET)
Primary Purpose
Non-small Cell Lung Cancer
Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Surgery
SABR
Sponsored by
About this trial
This is an interventional basic science trial for Non-small Cell Lung Cancer focused on measuring immune monitoring, T cell activation, early stage
Eligibility Criteria
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
Sites / Locations
- Erasmus MC Cancer InstituteRecruiting
- Antoni van Leeuwenhoek HospitalRecruiting
- VU Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Surgery
Radiotherapy
Arm Description
An anatomical surgical resection of primary tumor
Stereotactic Ablative Radiotherapy (SABR), outpatient treatment that is typically delivered in between 3-8 fractions
Outcomes
Primary Outcome Measures
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Number and activation status of peripheral CD8+ T cells
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Number and activation status of peripheral CD8+ T cells
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Number and activation status of peripheral CD8+ T cells
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Number and activation status of peripheral CD8+ T cells
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Number and activation status of peripheral CD8+ T cells
Secondary Outcome Measures
CD4/CD8 ratio in peripheral blood
CD4/CD8 ratio in peripheral blood
CD4/CD8 ratio in peripheral blood
CD4/CD8 ratio in peripheral blood
CD4/CD8 ratio in peripheral blood
number of regulatory T cells
number of regulatory T cells
number of regulatory T cells
number of regulatory T cells
number of regulatory T cells
Activation marker expression on T cells
Activation marker expression on T cells
Activation marker expression on T cells
Activation marker expression on T cells
Activation marker expression on T cells
Full Information
NCT ID
NCT02488850
First Posted
June 26, 2015
Last Updated
February 14, 2023
Sponsor
Erasmus Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02488850
Brief Title
Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage NSCLC
Acronym
HAMLET
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 2012 (undefined)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
immune monitoring, T cell activation, early stage
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Surgery
Arm Type
Active Comparator
Arm Description
An anatomical surgical resection of primary tumor
Arm Title
Radiotherapy
Arm Type
Active Comparator
Arm Description
Stereotactic Ablative Radiotherapy (SABR), outpatient treatment that is typically delivered in between 3-8 fractions
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Type
Radiation
Intervention Name(s)
SABR
Primary Outcome Measure Information:
Title
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Description
Number and activation status of peripheral CD8+ T cells
Time Frame
Baseline (week 0)
Title
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Description
Number and activation status of peripheral CD8+ T cells
Time Frame
Week 1
Title
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Description
Number and activation status of peripheral CD8+ T cells
Time Frame
Week 2
Title
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Description
Number and activation status of peripheral CD8+ T cells
Time Frame
Week 3
Title
Number of IFN-gamma/ Granzyme B producing CD8 T cells
Description
Number and activation status of peripheral CD8+ T cells
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
CD4/CD8 ratio in peripheral blood
Time Frame
Baseline
Title
CD4/CD8 ratio in peripheral blood
Time Frame
Week 1
Title
CD4/CD8 ratio in peripheral blood
Time Frame
Week 2
Title
CD4/CD8 ratio in peripheral blood
Time Frame
Week 3
Title
CD4/CD8 ratio in peripheral blood
Time Frame
Week 6
Title
number of regulatory T cells
Time Frame
Baseline
Title
number of regulatory T cells
Time Frame
Week 1
Title
number of regulatory T cells
Time Frame
Week 2
Title
number of regulatory T cells
Time Frame
Week 3
Title
number of regulatory T cells
Time Frame
Week 6
Title
Activation marker expression on T cells
Time Frame
Baseline
Title
Activation marker expression on T cells
Time Frame
Week 1
Title
Activation marker expression on T cells
Time Frame
Week 2
Title
Activation marker expression on T cells
Time Frame
Week 3
Title
Activation marker expression on T cells
Time Frame
Week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joachim G Aerts, MD, PhD
Phone
+31 10 70 43697
Email
j.aerts@erasmusmc.nl
Facility Information:
Facility Name
Erasmus MC Cancer Institute
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3015GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joachim Aerts, MD PhD
Phone
+31 10 704 3697
Email
j.aerts@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Joachim Aerts, MD PhD
First Name & Middle Initial & Last Name & Degree
Joost Hegmans, PhD
Facility Name
Antoni van Leeuwenhoek Hospital
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Egbert F Smit, MD PhD
Facility Name
VU Medical Center
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suresh Senan, MD PhD
12. IPD Sharing Statement
Citations:
PubMed Identifier
28345951
Citation
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.
Results Reference
derived
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Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage NSCLC
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