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

NCT05027165 | Unknown FDA Drug

• 1 other identifier: 20-502
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oncology; Biomarker; NSCLC, Stage III; Durvalumab; Chemoradiotherapy

Keywords

NSCLC; Stage III; Biomarker

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Predictive biomarkers for progression-free survival, overall survival, response rate, local and distant tumor control

  24 months

Study Arms (1)

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

Interventions

Non-interventional OTHER

No intervention

Observational group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• LMU Klinikum: lead
• Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Munich, Germany: collaborator
• Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany: collaborator
• Asklepios Lung Clinic, Munich-Gauting, Germany: collaborator
• Department of Radiology, University Hospital, LMU Munich, Munich, Germany: collaborator
• Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany: collaborator
• Institute for Medical Information Processing, Biometry and Epidemiology, LMU München, Munich, Germany: collaborator
• Department of Medicine II, University Hospital, LMU Munich, Munich, Germany: collaborator
• Immunoanalytics Research Group Tissue Control of Immunocytes, Helmholtz Center Munich, Munich, Germany: collaborator

Study Sites (1)

LMU University Hospital

Munich, Bavaria, 80336, Germany

Location

Related Publications (1)

• 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.

  PMID: 35958344 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Short circulating tumor total nucleic acid (ctTNA: ctDNA and ctRNA) within blood sample and possible mutations will be analysed at six different time points (blood sample will be collected 5-10 d before, after 15 fractions, at the end of concurrent chemoradiotherapy as well as 3-, 6- and 12 months after start of durvalumab). Blood samples will be evaluated using the Oncomine Pan-Cancer Cell free Assay (Life Technololgies) NGS (next generation sequencing).

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Farkhad Manapov, PhD MD

  LMU University hospital, Munich, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med Farkhad Manapov

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: August 30, 2021
• Study Start: November 7, 2020
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2025
• Last Updated: March 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)