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

Oncology Clinical Trial

— PRECISION  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05027165
• Other study ID #: 20-502
• Status: Active, not recruiting
• Start date: November 7, 2020
• Est. completion date: January 31, 2025

Study information

• Verified date: March 2023
• Source: LMU Klinikum
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Biomarker
• Carcinoma, Non-Small-Cell Lung
• Chemoradiotherapy
• Durvalumab
• NSCLC, Stage III
• Oncology

Intervention

Other:
• Non-interventional
No intervention

Locations

Country	Name	City	State
Germany	LMU University Hospital	Munich	Bavaria

Sponsors (9)

Lead Sponsor

Collaborator

LMU Klinikum

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

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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