Clinical Trials Logo

Clinical Trial Summary

Improving personalized cancer treatments and finding the best strategies to treat each patient relies on using new diagnostic technologies. Currently, for non small cell lung cancer (NSCLC), the methods used to decide who gets additional post radical (surgery or definite chemo-radiotherapy) treatment are suboptimal. Some patients get too much treatment, while others do not get enough. There is a new way to explore if there is any cancer left in a patient's body using circulating tumor DNA (ctDNA) detected in blood samples. This can help decide who needs more treatment. Even though many tests have been developed, it has yet to be determined which test performs best at relevant time points. The GUIDE.MRD consortium is a group of experts, including scientists, technology, and pharmaceutical companies. The consortium is working on creating a reliable standard for the ctDNA tests, validating their clinical utility, and collecting data to help decide on the best treatment for each patient. GUIDE.MRD-03-NSCLC is a part of the GUIDE.MRD project.


Clinical Trial Description

GUIDE.MRD-03-NSCLC is a part of WP3 of the overarching GUIDE.MRD project. Each study chair has a local clinical trial protocol where patients are recruited. After the end of recruitment, samples will be analyzed under the GUIDE.MRD consortium. The overall aim of GUIDE.MRD is to investigate the clinical utility of ctDNA analysis to predict and guide the choice of multi-modal therapies prospectively. The fundamental steps towards this aim are assessment and benchmarking of the many available ctDNA diagnostics to identify the best-suited tests for clinical application. Clinical samples will be used to benchmark ctDNA diagnostics and assess their true clinical performance. The samples should reflect clinical situations where the ctDNA diagnostics are particularly useful, such as post-operatively, post-adjuvant, during chemotherapy, and longitudinally during post-treatment surveillance. In these situations, ctDNA diagnostics could be used to either monitor treatment response (in case of MRD after surgery or definite chemoradiotherapy) or to identify relapse at an early time point. Based on ctDNA information, medical treatment could be changed, or radiology could be used to reveal the location of residual disease. The rationale for the observational clinical study GUIDE.MRD-03-NSCLC is to prospectively collect the clinical samples needed to enable assessment of the performance of ctDNA diagnostics in the setting of non small cell lung cancer (NSCLC). There are three main scenarios where ctDNA diagnostic is useful in NSCLC in a MRD setting: For this study stage III NSCLC will be included treated with curative intent using: 1. chemo-radiotherapy (concurrent or sequential) followed by adjuvant immunotherapy. This patient group is particularly relevant because adjuvant therapy is recommended for all stage III patients (in some countries for those with PD-L1>1% only), due to their high recurrence risk around 58%. Additionally, most of these do not need therapy at all, because they were already cured by chemo-radiotherapy alone, which leads to substantial overtreatment. Furthermore, the 58% of patients who recur despite both chemoradiotherapy and adjuvant immunotherapy, probably could benefit from further multimodal therapies. The challenge is, however, that currently there is no marker in clinical use that can identify those patients with residual disease and need for therapy. Circulating tumor DNA is potentially such a marker. 2. Neoadjuvant treatment followed by surgery (or radiotherapy with curative intent). In this setting up to 30% have a complete pathological response (pCR). These patients are probably cured by the neoadjuvant treatment alone, where surgery thus might have been avoided if the MRD biomarker would be sensitive enough. Patients that did not receive a pCR do worse with a median overall survival around 24 month even when they are treated with immunecheckpoint inhibitors adjuvantly. Better strategies for selecting patients and treatments are urgently needed here as well. Again ctDNA could be a marker that may help here when sensitive enough to select those that are negative for no adjuvant and those that are positive for ctDNA guided multimodality treatment. 3. Surgery followed by adjuvant chemotherapy and immunotherapy. Patients in this setting may be treated by immunotherapy adjuvantly only when PD-L1>1% (FDA) or PD-L1>50% (EMA). Also here recurrence risk is high around 50%. Additionally, most of these do not need therapy at all, because they were already cured by surgery alone, which leads to substantial overtreatment. Furthermore, the 50% of patients who recur despite both surgery and adjuvant therapy, probably could benefit from further multimodal therapies. The challenge is, however, that currently there is no marker in clinical use that can identify those patients with residual disease and need for therapy. Circulating tumor DNA is potentially such a marker. However, currently, it is unknown, which, if any,of the many different ctDNA diagnostics developed in recent years have the required, performance to provide clinical utility in the management in these settings of stage III NSCLC. Primary objectives: To assess the performance of ctDNA diagnostics using samples collected at four to five -landmark time-points "baseline"; "post neoadjuvant treatment"; "post-surgery or chemoradiotherapy"; "post-adjuvant therapy" and "at the end of study or disease progression".Sensitivity, specificity, and positive and negative predictive values of the ctDNA diagnostics will be determined to enable a head-to-head performance assessment and benchmarking of ctDNA diagnostics. Secondary objectives To assess the ctDNA stratified 3-year recurrence-free survival (RFS). To assess the lead time between ctDNA detection and clinical recurrence. To assess the capacity of the ctDNA diagnostics to predict response to neoadjuvant therapy. To assess the capacity of the ctDNA diagnostics to predict response to adjuvant therapy. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT06111807
Study type Observational [Patient Registry]
Source University Medical Center Groningen
Contact T.Jeroen N Hiltermann, MD, PhD
Phone 503644936
Email t.j.n.hiltermann@umcg.nl
Status Recruiting
Phase
Start date November 10, 2023
Completion date July 31, 2030

See also
  Status Clinical Trial Phase
Recruiting NCT06003075 - Induction Chemo-Nivo in Unresectable Stage III NSCLC Phase 2
Enrolling by invitation NCT04305613 - Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy
Not yet recruiting NCT05994339 - Radiotherapy Combined With Almonertinib for Stage III EGFR-Mutated Lung Cancer Phase 2/Phase 3
Not yet recruiting NCT06060964 - Enabling Remote Access to Breathe Easier: A Novel Approach to Improve Symptom Management Early Phase 1
Recruiting NCT04991025 - Adding Certolizumab to Chemotherapy + Nivolumab in People Who Have Lung Cancer That Can Be Treated With Surgery Phase 2
Completed NCT04825912 - Resilience Measurement in Older Adults With Late-Stage Lung Cancer N/A
Active, not recruiting NCT03141359 - Use of High Dose Radiation Followed by Chemotherapy and Radiation to Treat Locally Advanced NSCLC Phase 2
Recruiting NCT06086574 - Developing Circulating and Imaging Biomarkers Towards Personalised Radiotherapy in Lung Cancer
Recruiting NCT03872661 - Neoadjuvant IBI308, Bevacizumab, Plus Pemetrexed and Carboplatin Followed by Surgery in Unresectable Stage III NSCLC Phase 2
Not yet recruiting NCT05358691 - A Trial of AN0025 With Chemoradiation Therapy in Stage III NSCLC Participants Phase 1
Recruiting NCT06432972 - Accelerated Pulmonary Rehabilitation in the Preoperative Period N/A
Active, not recruiting NCT04364776 - Radiomic Signature as Predictive Marker of Response to Chemoradiation and Durvalumab in Stage III NSCLC.
Recruiting NCT05258448 - COr Loco-regional Advanced Lung Cancer Treated With Chemo-radiotherapy (COLA)
Recruiting NCT05996263 - Prognostic Value of Combined Approach Based on KEAP1/NFE2L2 Mutations and Pre-therapeutic FDG-PET/CT Radiomic Analysis in Advanced Non-small-cell Lung Cancer PDL1 ≥ 50% Treated With Pembrolizumab (PEMBROMIC)
Active, not recruiting NCT04003246 - Phase II Concurrent Durvalumab and Radiotherapy for for Stage III Non-Small Cell Lung Cancer Phase 2
Completed NCT04057196 - Self-System Therapy for Older Adults With Lung Cancer N/A