The Beneficial Value of PET/CT in the Follow-up of Stage III Non-small Cell Lung Cancer Patients

Stage III Non-small Cell Lung Cancer Clinical Trial

— NVALT31-PET  

Official title:

The Beneficial Value of 18F FDG PET/CT in the Follow-up of Stage III Non-small Cell Lung Cancer Patients: the NVALT31-PET Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06082492
• Other study ID #: 114319
• Secondary ID: NL83288.091.23
• Status: Recruiting
• Phase: N/A
• Start date: March 19, 2024
• Est. completion date: June 2029

Study information

• Verified date: September 2023
• Source: Radboud University Medical Center
• Contact: NVALT31-PET study team
• Phone: +31611469084
• Email: NVALT31PET[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the 3-year overall survival of stage III NSCLC patients during follow-up surveillance with 18F-Fluorodeoxyglucose Positron Emission Tomography/ Computerized Tomography (18F FDG PET/CT) versus follow-up with conventional CT surveillance. Participants will receive usual care until 3 years of follow-up (control group) with additional whole-body 18F FDG PET/CT scans during follow-up visits at 6 months, 12 months, 18 months, 24 months, and 36 months of follow-up in the intervention group. Other tasks include: - filling in quality of life (QOL) questionnaires at every time point; - participating in an interview evaluating the addition of the 18F FDG PET/CT scans (optional); - collecting blood at the follow-up time points for our secondary endpoint (optional). Researchers will compare the usual care control group with the intervention group to see if the additional 18F FDG PET/CT scans are (cost)-effective.

Description:

Stage III non-small cell lung cancer (NSCLC) patients are at high risk of developing recurrences (50-78%) during follow-up. With more effective treatments available for patients with oligometastatic disease, early detection of tumor recurrence can prolong survival and health-related quality of life and thereby lower the disease burden. With the use of 18F FDG PET/CT during follow-up, recurrences may be detected earlier at an oligometastatic state when curative-intent treatment is still possible. Primary objective: - The primary objective of this study is to compare the 3-year overall survival of stage III NSCLC patients during follow-up surveillance with 18F FDG PET/CT versus follow-up with conventional CT surveillance. The secondary objectives of this study are: - To compare the 2-year overall survival of stage III NSCLC patients during follow-up surveillance with 18F FDG PET/CT versus follow-up with conventional CT-based surveillance (interim analysis); - To compare the number of detected (symptomatic and asymptomatic) recurrences of stage III NSCLC patients during follow-up surveillance with 18F FDG PET/CT versus follow-up with conventional CT-based surveillance; - To compare the event-free survival of stage III NSCLC patients during follow-up surveillance with 18F FDG PET/CT versus follow-up with conventional CT-based surveillance; - To determine the cost-effectiveness of 18F FDG PET/CT versus conventional CT-based surveillance during follow-up of stage III NSCLC patients; - To compare the effect of 18F FDG PET/CT versus conventional CT-based surveillance on health-related quality of life during follow-up of stage III NSCLC patients; - To assess the beneficial value of ctDNA in the detection of recurrences during follow-up in stage III NSCLC patients; - To identify patients' experiences with the additional 18F FDG PET/CT scans in the follow-up of stage III NSCLC patients. - To assess differences in type of treatment following recurrence during follow-up in stage III NSCLC patients. Primary analyses will be performed on an intention-to-treat basis as well as per protocol. Kaplan-Meier curves with stratified log-rank 2-sided tests will be used to compare the survival between groups. In case of empty strata, strata will be collapsed. The clinical relevance of the difference will be primarily expressed in terms of 3-year survival of the intervention versus the control group.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 690
• Est. completion date: June 2029
• Est. primary completion date: April 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Eligible for this study are patients with stage III NSCLC (8th edition TNM Classification) who (are about to) start(ed) follow-up care (which may include adjuvant treatment) at a participating hospital. Patients may already be included during their curative intent treatment. Patients enter a screening period that runs until their randomization. Inclusion Criteria: To be eligible to participate in this study, a subject must meet all of the following

criteria at the timing of randomization:

• Cytological or histologically proven stage III non-small cell lung cancer before start of curative intent treatment
• Treated with curative intent and started follow-up care
• All adjuvant treatments are permitted as co-intervention during follow-up care
• Age 18 years or older
• ECOG Performance Status classification 0-2 at moment of inclusion
• Written and signed informed consent by the patient or patient's representative (with the understanding that consent may be withdrawn by the patient or patient's representative at any time without consequences to future medical care) Exclusion Criteria: A potential subject who meets any of the following criteria will be excluded from

participation in this study:

• Life expectancy shorter than 6 months at the end of curative intent treatment
• Evidence of recurrence after end of curative intent treatment and before randomization (4 months follow-up)
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the intervention or interpretation of HRQOL or other study results.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Stage III Non-small Cell Lung Cancer

Intervention

Diagnostic Test:
• 18F FDG PET/CT
Additional 18F FDG PET/CT scans during follow-up visits at 6, 12, 18, 24 and 36 months of follow-up.
• CT scan
CT of the thoracic region during follow-up visits at 6, 12, 18, 24 and 36 months of follow-up.

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Haaglanden Medisch Centrum	Den Haag
Netherlands	HagaZiekenhuis	Den Haag
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Treant	Emmen
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Tjongerschans ziekenhuis	Heerenveen
Netherlands	Tergooi MC	Hilversum	Utrecht
Netherlands	Dijklander Ziekenhuis	Hoorn
Netherlands	Radboudumc	Nijmegen
Netherlands	Bravis Ziekenhuis	Roosendaal
Netherlands	Franciscus Gasthuis & Vlietland	Schiedam
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Netherlands	Diakonessenhuis	Utrecht
Netherlands	St. Antonius Ziekenhuis	Utrecht & Nieuwegein

Sponsors (26)

Lead Sponsor

Collaborator

Radboud University Medical Center

Amphia Hospital, Amsterdam UMC, location VUmc, Antoni van Leeuwenhoek Hospital, Bravis Hospital, Canisius-Wilhelmina Hospital, Deventer Ziekenhuis, Diakonessenhuis, Utrecht, Dijklander Ziekenhuis, Elisabeth-TweeSteden Ziekenhuis, Franciscus &Vlietland, Gelderse Vallei Hospital, Gelre Hospitals, Groene Hart Ziekenhuis, Haaglanden Medical Centre, HagaZiekenhuis, Maasstadziekenhuis, Martini Hospital Groningen, Medisch Spectrum Twente, OLVG, St. Antonius Hospital, Streekziekenhuis Koningin Beatrix, Tergooi Hospital, Tjongerschans, Treant Zorggroep, UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival (OS) will be defined as time from end of curative intent treatment until death or loss to follow-up or end of study defined as 3 years after end of curative treatment.	3 years after end of curative intent treatment
Secondary	Number of detected symptomatic and asymptomatic recurrences	As seen on a scan and/or confirmed by biopsy	Up to 3 years after end of curative intent treatment
Secondary	Event-free survival (EFS)	Event-free survival will be defined as time from end of curative intent treatment until a recurrence (disease progression or relapse) or death or loss to follow-up, whichever comes first.	3 years after end of curative intent treatment
Secondary	Quality-adjusted life-years ((QALY's) for the cost-effectiveness analysis (CEA))	The European Quality of Life Five Dimension Five Level (EQ-5D-5L) will be used to measure quality-adjusted life-years. The scores will be transformed into health utilities using the Dutch tariff. QALY's will be estimated using the area under the curve method.	Up to 3 years after end of curative intent treatment
Secondary	Hospital and medical resource use (for the CEA)	Hospital resource use will be taken from the hospital records, and will include all diagnostic testing, treatment information, hospital visits, telephone and email consultations, and medication use. Other medical resource use as measured using an adapted version of the iMTA Medical Consumption Questionnaire (iMCQ) will provide information on visits to the GP or use of paramedical care. The prices associated with resource use will be derived from the Dutch guideline for costing, and tariffs and prices published by the Dutch Health authority. Total costs will be calculated by multiplying resource use by integral cost prices.	Up to 3 years after end of curative intent treatment
Secondary	Productivity losses (for the CEA)	The iMTA Productivity Costs Questionnaire (iPCQ) will provide information on productivity losses. Productivity losses will be values by the friction cost method.	Up to 3 years after end of curative intent treatment
Secondary	Health-related quality of life (HRQOL)	As measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) and lung module (EORTC-QLQ-LC13). The main HRQOL endpoints are physical functioning and the QLQ-C30 summary score. The QLQ-C30 summary score is calculated as the mean of the combined domains of the QLQ-C30 scale scores (excluding financial impact and a two-item global quality of life scale. All scale score are linearly transformed to 0-100, following EORTC guidelines. Effects on HRQOL will be investigated including all patients with at least one completed follow-up HRQOL questionnaire.	Up to 3 years after end of curative intent treatment collected around the follow-up scans.
Secondary	Patients' evaluation of the 18F FDG PET/CT scans	Semi-structured interviews with a selection of patients in the intervention group (optional)	Up to 3 years after end of curative intent treatment collected around the follow-up scans.
Secondary	Blood samples	Blood will be collected of intervention group patients in centers participating in the blood sample collection. For this, three cell-stabilizing tubes will be collected concurrently with the 18F FDG PET/CT scan, when the IV is inserted or at a planned blood test. The tubes will subsequently be sent to the sponsor within 24 hours, where the cell-stabilizing tubes will be centrifuged at room temperature for 10 min at 1600 g. Cell-free plasma will be stored in 5 mL aliquots at -80 °C until DNA isolation. Cell-free DNA will be isolated from 1 ml plasma for mutation analysis.	Up to 3 years after end of curative intent treatment collected around the follow-up scans.