PRedictive Value of Multiparametric Dynamic WB 18F-FDG-PET Imaging on a LAFOV System for FIRST-line Chemo-immunotherapy Efficacy in Advanced Non-small-cell Lung Cancer: PROFIL-1

Not yet recruiting

• Conditions: Non-Small Cell Lung Cancer

• Registration Number: NCT06738680
• Lead Sponsor: University Hospital, Brest

Brief Summary

Lung cancer is the leading cause of cancer deaths worldwide. Revolution of chemo-immunotherapy (CT-IO) in first-line of metastatic non-small-cell lung cancers (NSCLC) without actionable genomic alterations (AGAs) has dramatically improved prognosis, providing long response to a subset of patients. Because of a highly heterogeneous disease, majority of patients do not show long term benefit. Long axial field of view positron emission tomography (LAFOV-PET) scanner is a new emerging system allowing dynamic whole-body imaging with higher sensitivity, representing unique opportunity for oncological applications. The aim of this study is to determine if LAFOV-PET imaging biomarkers could early predict response to CT-IO in NSCLC.

Detailed Description

Lung cancer is the leading cause of cancer deaths worldwide. Revolution of chemo-immunotherapy (CT-IO) in first-line of metastatic non-small-cell lung cancers (NSCLC) without actionable genomic alterations (AGAs) has dramatically improved prognosis, providing long response to a subset of patients. Because of a highly heterogeneous disease, majority of patients do not show long term benefit. Long axial field of view positron emission tomography (LAFOV-PET) scanner is a new emerging system allowing dynamic whole-body imaging with higher sensitivity, representing unique opportunity for oncological applications. The aim of this study is to determine if LAFOV-PET imaging biomarkers could early predict response to CT-IO in NSCLC.

PROFIL-1 is a multicentre, single-arm, prospective non-interventional pilot study investigating the predictive value of multiparametric 18F-fluoro-deoxyglucose whole-body dynamic PET imaging on a LAFOV system for first-line CT-IO efficacy in advanced NSCLC, with a planned enrolment of 120 patients at 2 French sites. Adult patients with treatment-naïve advanced non-squamous or squamous NSCLC without AGAs and eligible for first-line CT-IO will be recruited for PROFIL-1. Patients will undergo LAFOV-PET before and after CT-IO induction. The primary objective is to evaluate predictive performance of a whole-body multiparametric analysis (radiomics and dynamics) in LAFOV-PET on CT-IO efficacy based on progression-free survival (PFS) per RECIST v1.1 by investigators. Secondary endpoints included correlations between imaging parameters and clinico-pathological characteristics, comparison between direct Patlak and indirect Patlak methods to determine dynamic parameters such as Ki (the net influx rate) and distribution volume (DV), number of tumor lesions and signal-to-noise ratio, objective response rate (ORR), overall survival (OS) and safety.

Study Timeline

• Study First Submitted: 2024-11-15
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-13
• Last Update Submitted: 2024-12-13
• Study First Posted: 2024-12-18
• Last Update Posted: 2024-12-18
• Study Start: 2025-01-30
• Primary Completion: 2026-01-30
• Study Completion: 2026-11-02

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Adult patients ≥ 18 years
• With advanced, non-operable, non-radiatable or metastatic NSCLC
• Treatment-naïve patients
• Eligible for first-line chemo-immunotherapy (anti-PD-1)
• Written Non-objection
• Eligible for LAFOV FDG-PET less than 21 days before initiation of treatment

Exclusion Criteria

• Minor patients <18 years
• Oncogenic addiction targetable in 1st line: EGFR, ALK, ROS1, RET
• Pregnancy or breast-feeding
• Other histology than NSCLC
• Ineligible for first-line chemo-immunotherapy
• PET-FDG Scan contraindications
• Refusal to participate

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1-year Progression-Free Survival	From date of chemo-immunotherapy initiation until the date of first documented progression or date of death, assessed up to 100 months.	The primary endpoint is 1-year Progression-Free Survival (PFS) rate. PFS is defined as the time from chemo-immunotherapy initiation to the date of the first documented event of tumor progression or death in the absence of disease progression, whichever came first, assessed up to 100 months.

Secondary Outcome Measures

Name	Time	Method
Measurement of Ki images	From baseline PET/CT before chemo immunotherapy in ml/min/100 g	Measurement of Ki images PET/CT parameters based on direct and indirect Patlak reconstruction methods with PBIF or IDIF in LAFOV-PET from baseline PET/CT before chemo immunotherapy
Measurement of distribution volume	From baseline PET/CT before chemo immunotherapy in L/kg	Measurement of distribution volume dynamic PET/CT parameter based on direct and indirect Patlak reconstruction methods with PBIF or IDIF in LAFOV-PET from baseline PET/CT before chemo immunotherapy
Correlation between quantitative dynamic and radiomic parameters and clinico-histopathological parameters	From baseline PET/CT before chemo immunotherapy	Correlation analyses between quantitative dynamic and radiomic PET derived parameters and clinico-histopathological parameters (clinical, biology, histology, genomic).
Contrast-to-noise ratio (CNR)	From baseline LAFOV PET/CT	Contrast-to-noise ratio (CNR) (indicating the image quality in the lesion)
Target-to-background ratio (TBR)	From baseline LAFOV PET/CT	Target-to-background ratio (TBR), defined as the ratio of the lesions\' SUVmax and the SUVmean of healthy liver tissue (background) determined for each reconstruction algorithm
Objective response rate (ORR)	From baseline LAFOV PET to end of 1 year of treatment	Objective response rate (ORR), defined as the proportion of patients experiencing an objective response (either complete response \[CR\] or partial response \[PR\]) as best response to CT-IO according to RECIST 1.1 criteria
Metabolic response rate (MRR)	From baseline LAFOV PET to end of 1 year of treatment	Metabolic response rate (MRR), defined as the proportion of patients experiencing a metabolic response (either complete metabolic response \[CMR\] or partial metabolic response \[PMR\]) as best response to CT-IO according to Positron Emission Tomography Response Criteria in Solid Tumors version 1.0 (PERCIST v1.0)
Overall Survival	From date of chemo-immunotherapy initiation until the date of death from any cause, assessed up to 100 months	Overall Survival, defined as the time from chemo-immunotherapy initiation until the date of death from any cause, assessed up to 100 months
Safety	From baseline LAFOV PET to end of 1 year of treatment	Safety and tolerability according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.; Patient reported outcomes according to EQ-5D-5L and EORTC QLQ-C30 (baseline, 3 months, 6 months, 12 months).

Trial Locations

Locations (2)

Brest University Hospital; 🇫🇷 Brest, France

Morlaix Hospital Center; 🇫🇷 Morlaix, France