Clinical trial NCT02488850: Determination of Peripheral Immune Cell Activity During Treatment With Either Surgery or Radiotherapy in Patients With Early Stage NSCLC
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
Overall status: COMPLETED
Phase: NA
Conditions: Non-small Cell Lung Cancer
Keywords: immune monitoring
T cell activation
early stage
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2015-07-02
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Number of IFN-gamma/ Granzyme B producing CD8 T cells
timeFrame: Baseline (week 0)
measure: Number of IFN-gamma/ Granzyme B producing CD8 T cells
timeFrame: Week 1
measure: Number of IFN-gamma/ Granzyme B producing CD8 T cells
timeFrame: Week 2
measure: Number of IFN-gamma/ Granzyme B producing CD8 T cells
timeFrame: Week 3
measure: Number of IFN-gamma/ Granzyme B producing CD8 T cells
timeFrame: Week 6
Secondary outcomes:
measure: CD4/CD8 ratio in peripheral blood
timeFrame: Baseline
measure: CD4/CD8 ratio in peripheral blood
timeFrame: Week 1
measure: CD4/CD8 ratio in peripheral blood
timeFrame: Week 2
measure: CD4/CD8 ratio in peripheral blood
timeFrame: Week 3
measure: CD4/CD8 ratio in peripheral blood
timeFrame: Week 6
measure: number of regulatory T cells
timeFrame: Baseline
measure: number of regulatory T cells
timeFrame: Week 1
measure: number of regulatory T cells
timeFrame: Week 2
measure: number of regulatory T cells
timeFrame: Week 3
measure: number of regulatory T cells
timeFrame: Week 6
measure: Activation marker expression on T cells
timeFrame: Baseline
measure: Activation marker expression on T cells
timeFrame: Week 1
measure: Activation marker expression on T cells
timeFrame: Week 2
measure: Activation marker expression on T cells
timeFrame: Week 3
measure: Activation marker expression on T cells
timeFrame: Week 6
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC Cancer Institute
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: VU Medical Center
Study officials:
References:
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.