Using Circulating Tumor DNA to Personalize Duration of Consolidation Durvalumab

NSCLC, Stage III Clinical Trial

Official title:

Using Circulating Tumor DNA to Personalize Duration of Consolidation Durvalumab in Patients With Inoperable Stage III Non-small Cell Lung Cancer: The Indiana Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05757843
• Other study ID #: CTO-IUSCCC-0749
• Status: Recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: Indiana University
• Contact: Ashley Vetor
• Phone: 3172742737
• Email: abozell[@]iu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• NSCLC, Stage III

Intervention

Diagnostic Test:
• Signatera ctDNA test
Prior to the 5th cycle of durvalumab, the first mandatory ctDNA test will be done. 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.

Drug:
• Durvalumab
All subjects will receive consolidation Durvalumab approximately every 4 weeks. Durvalumab will be stopped after two consecutive negative ctDNA analyses occur.

Locations

Country	Name	City	State
United States	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine if de-escalating number of Durvalumab cycles based on personalized ctDNA clearance has non-inferior 2-year PFS rate	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.	Baseline to 24 months
Secondary	Estimate the 24-month overall survival (OS) of patient treated with consolidation Durvalumab based on personalized ctDNA clearance	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.	Baseline to 24 months
Secondary	Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression	Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression of disease after receiving = 6 months of consolidation Durvalumab.	Baseline to 24 months