Prospective Evaluation of Immunological, Molecular-genetic, Image-based and Microbial Analyzes to Characterize Tumor Response and Control in Patients With Inoperable Stage III NSCLC Treated With Chemoradiotherapy Followed by Consolidation Therapy With Durvalumab (PRECISION)

Prospective Evaluation of Immunological, Molecular-genetic, Image-based and Microbial Analyzes to Characterize Tumor Response and Control in Patients With Inoperable Stage III NSCLC Treated With Chemoradiotherapy Followed by Consolidation Therapy With Durvalumab (PRECISION)

This non-interventional single-center explorative biomarker study aims at longitudinal comprehensive characterization (molecular genetics, immunological, morphological, image-based and microbial features) of the patient (host) and tumor as well as changes during standard treatment and in case of recurrent disease in inoperable stage III non-small cell lung cancer (NSCLC). Comprehensive analysis will include peripheral blood cellular and humoral immunophenotyping, circulating tumor DNA and gut/saliva microbiota analyses. 18F-FDG-PET/CT before, 6 weeks, 6- and 12-months after chemoradiotherapy as well as daily in course of radiation treatment cone-beam-CT and/or MRI imaging are included for morphological analysis. This study will provide valuable information of predictive biomarkers in patients with stage III NSCLC treated with durvalumab maintenance treatment after concurrent chemoradiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Oncology; NSCLC, Stage III; Chemoradiotherapy; Biomarker; Durvalumab
• Intervention / Treatment: Other: Non-interventional

Detailed Description

The study will enrol 40 patients with stage III inoperable non-small cell lung cancer (NSCLC) who received standard chemoradiotherapy followed by maintenance therapy with PD-L1 inhibition (durvalumab) according to the current European Medicines Agency (EMA) approval.

The oncological treatment is carried out according to the international standards of radiation oncology/medical oncology. These are implemented by the department of radiation oncology at the University Hospital Munich (LMU) in their SOPs. Therefore, all patients will be treated with concurrent platinum-based chemoradiotherapy followed by durvalumab maintenance treatment 12 months after the end of chemoradiotherapy at the department of radiation oncology (University Hospital Munich (LMU)). Comprehensive characterization of all patients includes immunophenotyping of peripheral blood mono-nuclear cells, ctDNA as well as gut/saliva microbiome analyses and will be performed before, after 15 fractions of radiotherapy, at the end of concurrent chemoradiotherapy as well as 3-, 6- and 12 months after start of durvalumab.

18F-FDG-PET/CT will be performed 5-10 d before start of radiotherapy, 6 weeks, 6 months,12 and 24 months after the end of chemoradiotherapy. Lung function will be assessed before start of radiotherapy, at the end and 6 weeks after chemoradiotherapy as well as 3-, 6- and 12, 18, 24 months after start of durvalumab.

Follow-up will be performed by the department of radiation oncology at the University Hospital Munich (LMU) according to the clinical SOPs.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Farkhad Manapov, PhD MD; Phone Number: 004989440057561; Email: Farkhad.Manapov@med.uni-muenchen.de
• Study Contact Backup: Name: Lukas Käsmann, MD; Phone Number: 004989440057561; Email: Lukas.Kaesmann@med.uni-muenchen.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Recruiting
      • LMU University Hospital
      • Contact: Farkhad Manapov, PhD MD; Phone Number: 004989440057561; Email: Farkhad.Manapov@med.uni-muenchen.de
      • Contact: Lukas Käsmann, MD; Phone Number: 004989440057561; Email: Lukas.Kaesmann@med.uni-muenchen.de
      • Principal Investigator: Farkhad Manapov, PhD MD
      • Sub-Investigator: Lukas Käsmann, MD
      • Sub-Investigator: Julian Taugner, MD
      • Sub-Investigator: Chukwuka Eze, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will enrol 40 patients with stage III inoperable non-small cell lung cancer (NSCLC) who received standard chemoradiotherapy followed by maintenance therapy with PD-L1 inhibition (durvalumab) at the department of radiation oncology, University Hospital Munich (LMU).

Description

Inclusion Criteria:

• Patient age ≥ 18 years
• Histologically/cytologically confirmed diagnosis of non-small-cell lung cancer (NSCLC)
• Patients with non-operable NSCLC in tumor stage III A/B/C after UICC 8
• Eligible for platinum-based concurrent chemoradiotherapy followed by durvalumab maintenance treatment
• No invasive carcinoma in the last five years.
• ECOG Performance Status 0-2
• Lung function parameters (before or after bronchodilation): FEV1 ≥ 1.0 L and/or DLCO-SB ≥ 40%
• A maximum of two cycles of induction chemotherapy are permissible before start of chemoradiotherapy

Exclusion Criteria:

• Simultaneous participation in another clinical trial
• Mixed histology of small-cell and non-small-cell lung cancer
• Brain metastases confirmed by a contrast enhanced cMRI
• Prior receipt of an immunotherapy or investigational medicinal product
• Previous exposure to an anti-PD-1 or anti-PD-L1 antibody
• Pneumonitis ≥ Grade 2 as a result of prior radio-/chemoradiotherapy
• Patients with a non-active disease in the last 5 years can be included, but only after consultation with the responsible investigator of the study or his representative
• Primary immunodeficiencies in previous history
• Prior Interstitial lung disease (ILD)
• Prior autoimmune disease
• Previous organ transplantation with subsequent therapeutic immunosuppression

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Observational group; In this cohort, 40 NSCLC patients with indication for chemoradiotherapy followed by durvalumab maintenance treatment ("standard of care") will be consecutively recruited. Comprehensive characterization of all patients includes immunophenotyping of peripheral blood mono-nuclear cells, ctDNA as well as gut/saliva microbiome analyses and will be performed before, after 15 fractions of radiotherapy, at the end of concurrent chemoradiotherapy as well as 3-, 6- and 12 months after start of durvalumab. 18F-FDG-PET/CT will be performed 5-10 d before start of radiotherapy, 6 weeks, 6 months,12 and 24 months after the end of radiochemotherapy. Lung function will be asssed before start of radiotherapy, at the end and 6 weeks after chemoradiotherapy as well as 3-, 6- and 12, 18, 24months after start of durvalumab.

Other: Non-interventional; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive biomarker for progression-free survival at 12 and 24 months	To identify early immunological and morphological biomarkers and their dynamic changes to predict progression-free survival at 12 and 24 months.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive biomarkers for progression-free survival, overall survival, response rate, local and distant tumor control	To identify predictive biomarkers for progression-free survival at 6 and 18 months after chemoradiotherapy and overall survival and response rate, local and distant tumor control at 6 weeks, 6-, 12-, 18 and 24 months from the end of chemoradiotherapy.	24 months

Collaborators and Investigators

• Sponsor: LMU Klinikum
• Collaborators: Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Munich, Germany; Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany; Asklepios Lung Clinic, Munich-Gauting, Germany; Department of Radiology, University Hospital, LMU Munich, Munich, Germany; Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany; Institute for Medical Information Processing, Biometry and Epidemiology, LMU München, Munich, Germany; Department of Medicine II, University Hospital, LMU Munich, Munich, Germany; Immunoanalytics Research Group Tissue Control of Immunocytes, Helmholtz Center Munich, Munich, Germany
• Investigators: Principal Investigator: Farkhad Manapov, PhD MD, LMU University hospital, Munich, Germany

Publications and helpful links

General Publications

• Kasmann L, Taugner J, Eze C, Nieto A, Pelikan C, Florsch B, Kenndoff S, Hofer TP, Nossner E, Schulz C, Unterrainer M, Tufman A, Klauschen F, Jung A, Neumann J, Kumbrink J, Reinmuth N, Bartenstein P, Belka C, Manapov F. Prospective evaluation of immunological, molecular-genetic, image-based and microbial analyses to characterize tumor response and control in patients with unresectable stage III NSCLC treated with concurrent chemoradiotherapy followed by consolidation therapy with durvalumab (PRECISION): protocol for a prospective longitudinal biomarker study. Transl Lung Cancer Res. 2022 Jul;11(7):1503-1509. doi: 10.21037/tlcr-21-1010.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 7, 2020
• Primary Completion (ANTICIPATED): March 31, 2023
• Study Completion (ANTICIPATED): March 31, 2023

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (ACTUAL): August 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Biomarker; NSCLC; Stage III
• 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: 20-502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data is available on request due to privacy/ethical restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No