NSCLC, Stage III
Conditions
Brief summary
This research aims to incorporate ctDNA analysis into clinical practice to individualize therapy in patients with stage III NSCLC by moving to a treatment-by-marker based approach (as opposed to treatment based on clinical or radiographic evidence of disease).
Detailed description
There is a critical need to identify MRD to determine which patients benefit from checkpoint inhibitor therapy and to optimize and personalize the duration of consolidation Durvalumab. The long-term goal is to incorporate ctDNA analysis into clinical practice to individualize therapy in patients with stage III NSCLC by moving to a treatment-by-marker based approach (as opposed to treatment based on clinical or radiographic evidence of disease). This approach may spare a subset of patients from treatment with unnecessarily excessive cycles of consolidation immunotherapy if they are already cured with CRT alone and individualize the duration of consolidation immunotherapy in patients not cured with CRT. The study team also seek to identify early in the treatment course, patients who are destined not to be cured with consolidation immunotherapy so that alternative strategies can be tested when tumor burden is low.
Interventions
DIAGNOSTIC_TESTSignatera ctDNA test
The first mandatory ctDNA test will be done at screening for the bespoke ctDNA profiling. The next mandatory ctDNA test will be completed prior to the 5th cycle of consolidation Durvalumab. ctDNA testing will be repeated approximately every 4 weeks until two consecutive negative analyses occur. ctDNA testing will be otherwise discontinued after progressive disease or after up to 1 year of consolidation treatment per standard medical practice is considered complete, whichever occurs first.
DRUGDurvalumab
All subjects will receive consolidation Durvalumab approximately every 4 weeks. Durvalumab will be stopped after two consecutive negative ctDNA analyses occur.
Sponsors
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age ≥ 18 years Ability to provide written informed consent and HIPAA authorization Patients with inoperable or unresectable stage III NSCLC who are planning to receive concurrent CRT followed by consolidation Durvalumab OR Patients with inoperable or unresectable stage III NSCLC who have previously received concurrent CRT and are planning or currently receiving C1-4 consolidation durvalumab Must have viable tissue for ctDNA profiling, (fresh or archived tissue)
Exclusion criteria
Patient unwilling to provide tissue and blood samples for ctDNA testing. Patient has contraindications to treatment with concurrent CRT and/or consolidation Durvalumab. Patients with any other active cancer; excluding squamous cell or basal cell cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine if de-escalating number of Durvalumab cycles based on personalized ctDNA clearance has non-inferior 2-year PFS rate | Baseline to 24 months | Determine if de-escalating the number of Durvalumab cycles based on personalized ctDNA clearance guidance to at least 6 cycles after CRT in stage III non-resectable NSCLC has non-inferior 2-year PFS rate compared with historical control of empirically treating stage III non-resectable NSCLC for 1 year of Durvalumab after CRT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimate the 24-month overall survival (OS) of patient treated with consolidation Durvalumab based on personalized ctDNA clearance | Baseline to 24 months | Estimate the 24-month overall survival (OS) of patient treated with consolidation Durvalumab based on personalized ctDNA clearance guidance for at least 6 cycles after CRT in stage III non-resectable NSCLC. |
| Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression | Baseline to 24 months | Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression of disease after receiving ≥ 6 months of consolidation Durvalumab. |
Outcome results
None listed