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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)

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ClinicalTrials.gov Identifier: NCT05027165
Recruitment Status : Recruiting
First Posted : August 30, 2021
Last Update Posted : September 8, 2021
Sponsor:
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
Information provided by (Responsible Party):
Farkhad Manapov, LMU Klinikum

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.

Condition or disease Intervention/treatment
Oncology Biomarker NSCLC, Stage III Durvalumab Chemoradiotherapy 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.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
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)
Actual Study Start Date : November 7, 2020
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

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




Primary Outcome Measures :
  1. Predictive biomarker for progression-free survival at 12 and 24 months [ Time Frame: 24 months ]
    To identify early immunological and morphological biomarkers and their dynamic changes to predict progression-free survival at 12 and 24 months.


Secondary Outcome Measures :
  1. Predictive biomarkers for progression-free survival, overall survival, response rate, local and distant tumor control [ Time Frame: 24 months ]
    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.


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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05027165


Contacts
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Contact: Farkhad Manapov, PhD MD 004989440057561 Farkhad.Manapov@med.uni-muenchen.de
Contact: Lukas Käsmann, MD 004989440057561 Lukas.Kaesmann@med.uni-muenchen.de

Locations
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Germany
LMU University Hospital Recruiting
Munich, Bavaria, Germany, 80336
Contact: Farkhad Manapov, PhD MD    004989440057561    Farkhad.Manapov@med.uni-muenchen.de   
Contact: Lukas Käsmann, MD    004989440057561    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         
Sponsors and Collaborators
LMU Klinikum
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
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Principal Investigator: Farkhad Manapov, PhD MD LMU University hospital, Munich, Germany
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Responsible Party: Farkhad Manapov, PD Dr. med Farkhad Manapov, LMU Klinikum
ClinicalTrials.gov Identifier: NCT05027165    
Other Study ID Numbers: 20-502
First Posted: August 30, 2021    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data is available on request due to privacy/ethical restrictions.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Farkhad Manapov, LMU Klinikum:
NSCLC
Stage III
Biomarker
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases