Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive prior to surgery (lobectomy) SABR.

Patients receive prior to surgery (lobectomy) SABR + 2 rounds of pembrolizumab

Prior to surgery (lobectomy), patients receive stereotactic ablative radiotherapy.

SABR

Prior to surgery (lobectomy), patients receive stereotactic ablative radiotherapy + 2 rounds of pembrolizumab

SABR + pembrolizumab

Eveline A van de Stadt, MD

Anna-Larissa N Niemeijer, MD

E.F. Smit, MD, PhD

A.J. de Langen, MD, PhD

This study aims to evaluate the safety and mechanisms of action of the trimodality treatment (radiotherapy, immunotherapy and surgery) in early-stage non-small cell lung cancer. Half of the patients will receive stereotactic ablative radiotherapy followed by 2 cycles of immunotherapy (pembrolizumab); the other half will not receive the immunotherapy treatment. After treatment, both groups will continue treatment according to guidelines and will undergo surgery (lobectomy).

An open label randomized exploratory study of the safety and mechanisms of action of combined treatment with SBRT and immunotherapy (pembrolizumab, anti-PD1) for early stage NSCLC.

Intervention:

Patients will be randomized between SBRT with or without 2 cycles of pembrolizumab treatment (starting on the first day of radiotherapy). The patients will undergo a lobectomy with hilar and mediastinal lymph node dissection after SBRT +/- pembrolizumab treatment. Translational research to explore the immune mechanism of action will include biological imaging with immuno-PET (positron emission tomography). Expression rates and activation states of immune effector subsets will be assessed in tumor core biopsy specimens, peripheral blood and tumor draining lymph nodes (TDLNs) by means of fine needle aspirates of TDLNs.

Main study parameters/endpoints:

To assess the safety of combined SBRT and pembrolizumab treatment in early stage NSCLC and to identify the immunological mechanism of action.

Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery

Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery: Exploring Safety and Immunological Proof of Principle.

Safety of the combination of SBRT and pembrolizumab will be assessed by the percentage of ≥3 pneumonitis. When combined SBRT and pembrolizumab treatment results in NCIC-CTC grade ≥3 pneumonitis in ≤10% of patients, the combination is regarded as safe. Serious adverse events will be recorded to assess both incidence and severity.

PD-1 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.

PD-L1 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.

CD4 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.

CD8 expression in tumor tissue, TDLN's and peripheral blood.

FoxP3 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.

Ki67 expression in tumor tissue, tumordraining lymphnodes and peripheral blood.

Cell count of the individual immune cells in tumordraining lymphnodes and non-tumordraining lymphnodes

SUVmax will be measured in all tumor lesions, enlarged lymph nodes and liver, kidneys, lungs, spleen and left ventricle of the heart.

SUVpeak will be measured in all tumor lesions, enlarged lymph nodes and liver, kidneys, lungs, spleen and left ventricle of the heart.

SUVmean will be measured in all tumor lesions, enlarged lymph nodes and liver, kidneys, lungs, spleen and left ventricle of the heart.

The pre- and post SBRT +/- pembrolizumab CT scans will be assessed for HU density and f-air values

The pre- and post SBRT +/- pembrolizumab CT scans will be assessed for and f-air values

The data of the PET-scan will be analyzed and compared to the blood and tissue samples to find a correlation between findings.

SUV are values used to describe PET-data. irAE's are specific adverse events. This outcome aims to correlate the (possible) irAE's with the PET-data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery	NCT03446911	NSCLC, Stage I	SABR SABR + pembroli...	18 Years -	Amsterdam UMC, location VUmc
Combining SBRT and Immunotherapy in Early Stage NSCLC Patients Planned for Surgery	NCT03446911	NSCLC, Stage I	SABR SABR + pembroli...	18 Years -	Amsterdam UMC, location VUmc

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