Clinical trial NCT05027165: 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
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)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Oncology
Biomarker
NSCLC, Stage III
Durvalumab
Chemoradiotherapy
Keywords: NSCLC
Stage III
Biomarker
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
Collaborators: name: Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Munich, Germany
name: Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany
name: Asklepios Lung Clinic, Munich-Gauting, Germany
name: Department of Radiology, University Hospital, LMU Munich, Munich, Germany
name: Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
name: Institute for Medical Information Processing, Biometry and Epidemiology, LMU München, Munich, Germany
name: Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
name: Immunoanalytics Research Group Tissue Control of Immunocytes, Helmholtz Center Munich, Munich, Germany
First posted: 2021-08-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Predictive biomarker for progression-free survival at 12 and 24 months
timeFrame: 24 months
Secondary outcomes:
measure: Predictive biomarkers for progression-free survival, overall survival, response rate, local and distant tumor control
timeFrame: 24 months
Other outcomes:
Locations:
city: Munich
country: Germany
facility: LMU University Hospital
state: Bavaria
Study officials:
affiliation: LMU University hospital, Munich, Germany
name: Farkhad Manapov, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.