Clinical trial NCT05426668: Validation of the TheraSure CNI-Monitor Under Immuno-checkpoint-therapy (hereinafter: "immunotherapy") in NSCLC in Palliative Therapy
Official title: Validation of the TheraSure CNI-Monitor Under Immuno-checkpoint-therapy (hereinafter: "immunotherapy") in NSCLC in Palliative Therapy
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: NSCLC
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
Collaborators: name: Chronix Biomedical Corporation
First posted: 2022-06-22
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with incurable stage III or stage IV NSCLC on immunotherapy

Brief summary: This is a prospective, non-interventional, national study planned at three centers for 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 CNI 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 CNI 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%.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent form
* Age ≥18 years
* NSCLC, non-curatively treatable stage III or stage IV with palliative treatment indication
* Immunocheckpoint-therapy for malignant disease (Immunotherapy as monotherapy, double immunotherapy or combination with chemotherapy)

Exclusion Criteria:

* Person is unable to understand the nature, importance and scope of the clinical trial
* Participation in an interventional study
* Hb value \<9g/dl

Primary outcomes:
measure: PD
timeFrame: 6 months
Secondary outcomes:
measure: PFS
timeFrame: 6 months
measure: OS
timeFrame: 6 months
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg
Study officials:
References: