Immune Boost In Non-Small Cell Lung Cancer (RadImmune)

A Randomized Phase II Study of Radiation Induced Immune Boost in Operable Non-small Cell Lung Cancer

Insufficient migration and activation of tumour specific effector T cells seems to be the one important reason for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Radiation: Preoperative radiation

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69126
    • Department of Thoracic Surgery, Thoraxklinik, University Hospital Heidelberg
  • Heidelberg, Germany, 69126
    • German Cancer Research Centre and Clinic for Radiation Oncology of the University of Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically proven clinical stage I to IIA pulmonary adenocarcinoma
• Lung tumor is felt to be curatively resectable by the treating physicians
• Sufficient pulmonary function for lobectomy according to current guidelines
• The patient is free of distant metastases as confirmed by contrast-enhanced chest and upper abdomen CT-scan and by contrast-enhanced CT or MRI of the brain
• Age over 50years at the time of consent due to federal radiation protection law
• In female patients of childbearing potential there must be a negative pregnancy test
• Eastern Cooperative Oncology Group performance status of 0,1, 2 or 3 at the time of randomization
• Patients who the investigator believes can and will comply with the requirements of this protocol
• Written informed consent according to good clinical practise and national/regional regulations

Exclusion Criteria:

• The patient shows clinical signs of pneumonia
• The patient receives immunosuppressive drugs (alkylating agents, antimetabolites, methotrexate, azathioprine, mercaptopurine, cytotoxic antibodies, ciclosporin, tacrolimus, sirolimus, interferon, mycophenolate, small biological agents)
• The patient has been diagnosed with a potential immune mediated disease
• Elevated blood leukocyte count or erythrocyte sedimentation rate
• Pregnancy
• The patient has received any cancer specific treatment, including radiotherapy, immunotherapy, hormonal therapy or chemotherapy
• The patient is diagnosed with a concomitant malignancy and/or has a history of malignancy within the past five years or has had a malignancy that has been in complete remission for less than 5 years
• The patient needs chronic long term oxygen therapy
• The patient has undergone splenectomy
• The patient is known to be HIV positive
• The patient has an uncontrolled bleeding disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No radiation; Lobectomy for lung cancer without preoperative radiation
Experimental: Preoperative radiation; Lobectomy for lung cancer with preoperative radiation	Radiation: Preoperative radiation; Lobectomy for lung cancer following preoperative radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cluster of differentiation (CD)8+ T cells in resected NSCLC	Frequencies of CD8+ T cells in resected NSCLC tumors determined by immunohistochemistry	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T cell subtypes in resected NSCLC	Frequencies of CD3+, CD4+, CD45RO and Foxp3+ T cells in resected NSCLC tumors determined by immunohistochemistry and flow cytometry	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor reactive T cells	Frequencies of tumor reactive T cells in blood and bone marrow before radiotherapy and after surgery	3 months

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Collaborators: German Cancer Research Center; Heidelberg University
• Investigators: Principal Investigator: Seyer Safi, MD, PhD, University Hospital Heidelberg; Principal Investigator: Hans Hoffmann, MD, PhD, University Hospital Heidelberg; Principal Investigator: Peter Huber, MD, PhD, German Cancer Research Centre

Publications and helpful links

General Publications

• Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, Klapproth K, Schakel K, Garbi N, Jager D, Weitz J, Schmitz-Winnenthal H, Hammerling GJ, Beckhove P. Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 2013 Nov 11;24(5):589-602. doi: 10.1016/j.ccr.2013.09.014. Epub 2013 Oct 24.
• Safi S, Beckhove P, Warth A, Benner A, Roeder F, Rieken S, Debus J, Dienemann H, Hoffmann H, Huber PE. A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer (RadImmune trial). BMC Cancer. 2015 Dec 19;15:988. doi: 10.1186/s12885-015-2006-2.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): February 1, 2020
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: May 27, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 18, 2014

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: S-576/ 2013