Radiomic Signature as Predictive Marker of Response to Chemoradiation and Durvalumab in Stage III NSCLC.

Blue Sky Radiomics: an Observational Study on Computed Tomography as an Image-based Predictive Marker of Response to Chemoradiation Followed by Durvalumab in Stage III Unresectable Non-small Cell Lung Cancer (NSCLC).

The introduction of maintenance immunotherapy with the anti PD-L1 inhibitor durvalumab opened a new therapeutic window for stage III NSCLC patients who achieve at least stable disease after chemo-radiation, as shown by the randomized phase 3 PACIFIC study. However, still half of the patients do progress at 12 months (up to 70% at 18 months). In this study, the investigators aim to test a non-invasive image-based approach, namely a "radiomics" platform, as a tool to define a higher or lower likelihood of response to chemo-radiation and durvalumab. For this purpose, we will retrospectively and prospectively collect and analyze a cohort of at least 70 stage III NSCLC patients treated with CT-RT followed by maintenance durvalumab.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer; Lung Cancer Stage III
• Intervention / Treatment: Drug: Durvalumab

Detailed Description

Specific aim (one):

To collect and analyze CT scans at diagnosis and after chemoradiation, and assign them to a specific radiomic signature (blind assessment).

Specific aim (two):

- To correlate the radiomics signatures to clinical outcome: the main measure will be progression-free survival at 6 months, the second will be overall survival at 24 months.

This is an observational longitudinal retrospective/prospective study.

Criteria for study entry:

• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
• Age 18-80
• Stage IIIA-C disease judged to be unresectable by a multidisciplinary team including pulmonologists, thoracic surgeons, medical and radiation oncologists.
• Signed informed consent

Exclusion criteria:

• Inability to sign the informed consent
• Absence of analyzed CT images

Treatment:

As per indication, patients should have received a thoracic radiation dose of at least 54 Gy to the primary tumor and lymph nodes; all techniques are allowed. Conventional fractionation or mild hypofractionation is also allowed. All different platinum-based chemotherapy regimens are admitted for the present study in combination with radiotherapy, given either concomitantly or sequentially, according to International Guidelines for combination therapy in locally advanced NSCLC.

Radiomic data extraction: after a pilot harmonization study phase, all CT scans will be analyzed using two different pre-defined signatures. The first one was developed by the Institut Gustave Roussy, Paris, and the second one by Radiomics (Liegi, Belgium). These two signatures have been either linked to response to anti PD1 or to chemoradiation alone.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Stage III unresectable non-small cell lung cancer patients undergoing chemoradiation followed by durvalumab.

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
• Age 18-80
• Stage IIIA-IIIB-IIIC disease judged to be unresectable by a multidisciplinary team including pulmonologists, thoracic surgeons, medical and radiation oncologists.
• Signed informed consent

Exclusion Criteria:

• Inability to sign the informed consent
• Absence of analyzed CT images

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Proportion of patients without disease progression (local, distant, or both) at 6,12,18 and 24 months, and median Progression-Free survival.	24 months from the end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Proportion of patients alive at 6, 12, 18 and 24 months, and median overall survival	24 months from the end of radiotherapy

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Matteo

Publications and helpful links

General Publications

• Cabini RF, Brero F, Lancia A, Stelitano C, Oneta O, Ballante E, Puppo E, Mariani M, Ali E, Bartolomeo V, Montesano M, Merizzoli E, Aluia D, Agustoni F, Stella GM, Sun R, Bianchini L, Deutsch E, Figini S, Bortolotto C, Preda L, Lascialfari A, Filippi AR. Preliminary report on harmonization of features extraction process using the ComBat tool in the multi-center "Blue Sky Radiomics" study on stage III unresectable NSCLC. Insights Imaging. 2022 Mar 7;13(1):38. doi: 10.1186/s13244-022-01171-1.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Estimated): December 15, 2023
• Study Completion (Estimated): December 15, 2024

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; radiotherapy; durvalumab; radiomics
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: 20200008978

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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