Validation of the TheraSure CNI Monitor Under Immune Checkpoint Therapy (Hereinafter: "Immunotherapy") in NSCLC in Palliative Therapy

NSCLC Clinical Trial

— CNI-Monitor  

Official title:

Validation of the TheraSure CNI Monitor Under Immune Checkpoint Therapy (Hereinafter: "Immunotherapy") in NSCLC in Palliative Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05426668
• Other study ID #: 2021-01519
• Status: Not yet recruiting
• Start date: August 2022
• Est. completion date: August 2024

Study information

• Verified date: June 2022
• Source: University Medical Center Goettingen
• Contact: Jessica Halfen, Dr.
• Phone: +495513962362
• Email: jessica.halfen[@]med.uni-goettingen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a prospective, non-interventional, national study planned at three centers in patients with non-curative NSCLC receiving immunotherapy.

At present, PD-L1 expression or tumor mutation burden serve as surrogate parameters for response to immunotherapy. However, the problem for clinicians is that not all patients with positive findings respond to this form of therapy.

Cell-free DNA (cf-DNA) can be detected in blood plasma. Tumor cells almost always have chromosomal instabilities (or "copy-number variations" (CNV)), which can be detected using next-generation sequencing (NGS), also in the cf-DNA. These CNV can be quantified and given as a cf-DNA copy number instability score (CNI value). TheraSure CNI Monitor is a highly sensitive method that can detect as little as 0.5% tumor DNA in plasma.

In preliminary work in a cohort of 56 patients with various types of cancer (including:

breast, colon, lung, ovary, melanoma) in advanced stages, the TheraSure CNI monitor was already evaluated in the monitoring of immunotherapy. In 51 of the 56 patients, increased CKD values were measured before the start of therapy compared to a normal group of 126 individuals. To predict the success of the therapy, further blood samples were used after the first and second therapy cycle and threshold values were set for the minimal expected decrease in the CKD value in the event of therapy response. A therapy failure could be predicted with a high positive predictive value, cases of hyperprogression could be detected earlier than by routine imaging. In addition, pseudoprogression could be distinguished from true progression using the CRF value.

The CNI monitor on cell-free DNA is to be used prospectively in 170 patients. The primary objective of the study is the prediction of primary progression under immunomonotherapy (defined as PD within 6 months after RECIST) with a predictive value for progression (PPV) of ≥50%.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 170
• Est. completion date: August 2024
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent form

• Patients with NSCLC, non-curatively treatable stage III and stage IV in palliative treatment situation with immunotherapy (in the sense of monotherapy, double immunotherapy or combination with chemotherapy)

Exclusion Criteria:

• Persons unable to understand the nature, importance and scope of the clinical trial

• Participation in an interventional study

• Age <18 years

• Hb value <9g/dl

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Other:
• No Intervention
No Intervention

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Karsten Gavenis

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PD	The TheraSure CKD monitor predicts primary progression on immunomonotherapy (defined as PD within 6 months of RECIST) with a predictive value for progression (PPV) of =50%.	6 months
Secondary	PFS	The TheraSure CRF monitor predicts progression-free survival (PFS) in cancer patients receiving immunotherapy. The aim is to determine a significantly different (p<.05) hazard ratio with a describable dichotomized result of the cell-free tumor DNA.	6 months
Secondary	OS	The TheraSure CRI Monitor predicts overall survival (OS) in cancer patients receiving immunotherapy. The aim is to determine a significantly different (p<.05) hazard ratio with a describable dichotomized result of the cell-free tumor DNA.	6 months