Using Circulating Tumor DNA to Personalize Duration of Consolidation Durvalumab

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

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).

Study Overview

• Status: Withdrawn
• Conditions: NSCLC, Stage III
• Intervention / Treatment: Drug: Durvalumab; Diagnostic test: Signatera ctDNA test

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
      • Principal Investigator: Nasser Hanna, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Consolidation to Durvalumab; All subjects will receive consolidation Durvalumab approximately every 4 weeks. 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. 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Nasser Hanna, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Estimated): September 13, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: CTO-IUSCCC-0749

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No