Using Circulating Tumor DNA to Personalize Duration of Consolidation Durvalumab
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Consolidation to Durvalumab All subjects will receive consolidation Durvalumab approximately every 4 weeks. Prior to the 5th cycle the first mandatory ctDNA test will be done. If it's negative and the subsequent test 4 weeks later prior to cycle 6 is negative, then Durvalumab will be stopped otherwise subject will continue consolidation durvalumab until 2 negative ctDNA analyses performed approximately 4 weeks apart or up to 1 year of consolidation per standard medical practice is complete. |
Diagnostic Test: Signatera ctDNA test
All subjects will receive consolidation Durvalumab approximately every 4 weeks. Prior to the 5th cycle the first mandatory ctDNA test will be done. If it's negative and the subsequent test 4 weeks later prior to cycle 6 is negative, then Durvalumab will be stopped otherwise subject will continue consolidation durvalumab until 2 negative ctDNA analyses performed approximately 4 weeks apart or up to 1 year of consolidation per standard medical practice is complete.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Patients with inoperable or unresectable stage III NSCLC who have previously received concurrent CRT if they enroll prior to receiving 1st cycle of Durvalumab are eligible.
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Indiana University Melvin and Bren Simon Comprehensive Cancer Center | Indianapolis | Indiana | United States | 46202 |
Sponsors and Collaborators
- Indiana University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CTO-IUSCCC-0749