Adjuvant Chemotherapy in Patients With Intermediate or High Risk Stage I or Stage IIA Non-squamous Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Randomized Prospective Trial of Adjuvant Chemotherapy in Patients With Completely Resected Stage I or IIA Non-Squamous Non-Small Cell Lung Cancer Identified as Intermediate or High Risk by a 14-Gene Prognostic Assay

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01817192
• Other study ID #: EC-120888
• Secondary ID: IFCT-2002
• Status: Recruiting
• Phase: N/A
• Start date: September 11, 2020
• Est. completion date: May 15, 2025

Study information

• Verified date: December 2023
• Source: Encore Clinical
• Contact: Michael Mann, MD
• Phone: 650-535-0030
• Email: mmann[@]encoreclinical.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The optimal treatment for Stage I or Stage IIA non-small cell lung cancer (NSCLC) remains controversial. Radiographic surveillance alone has been recommended for stage I and stage IIA patients after the tumor is removed surgically from the lung, and this standard has been based on the fact that no previous clinical trial has demonstrated a benefit for Stage I or Stage IIA NSCLC patients who receive post-operative chemotherapy. These patients, however, have a substantial risk of death within five years after operation, ranging from approximately 30% to 45%, largely due to metastatic disease that is present immediately after surgery but that is undetectable by conventional methods. Some leading organizations therefore currently recommend post-operative chemotherapy as an alternative standard of care in Stage I or Stage IIA NSCLC patients who are considered to be at particularly high-risk. Up until now, however, there has not been a well-validated means to identify stage I and stage IIA NSCLC patients at high risk of death within five years after operation. A new prognostic tool, a 14-Gene Prognostic Assay, which has been validated and definitively demonstrated in large scale studies to identify intermediate and high-risk stage I or Stage IIA patients with non-squamous NSCLC, is now available to all clinicians through a CLIA-certified laboratory. It is therefore now possible to compare the outcomes of patients randomly assigned to one or the other of these competing standards of care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1050
• Est. completion date: May 15, 2025
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Written informed consent

Age = 18 years

Able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy according to local institutional standards and likely compliance with follow-up for anticipated length of study (i.e. 5 years from the initiation of enrollment).

Willing to be randomized to chemotherapy.

Histologically documented completely resected (R0) Stage I or IIA non-squamous NSCLC (per 8th edition, TNM staging system)

Adequate tissue sample for the 14-Gene Prognostic Assay

Life expectancy excluding NSCLC diagnosis = 5 years

ECOG performance status 0-1

Completely healed incisions

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Adjuvant Chemotherapy
Patients who have undergone complete resection of NSCLC that has been documented histologically to be non-squamous and that is pathological Stage I or IIA, will undergo testing with the 14-Gene Prognostic Assay. Patients determined to be intermediate or high risk and who meet all eligibility criteria will be randomized either to observation or to four cycles of adjuvant therapy with a standard NSCLC platinum-based doublet.

Other:
• Radiographic surveillance
Serial radiographic surveillance is a current standard of care for Stage I or Stage IIA lung cancer. All intermediate or high risk patients randomized to observation or chemotherapy will have routine CT Scans at 6 month intervals until 5 years after enrollment and at yearly intervals thereafter until the end of the study period.
• 14-Gene Prognostic Assay
This CLIA-approved assay is a standard tool that is now available to all clinicians to improve the prognostic evaluation of patients after resection of Stage I or Stage IIA non-squamous NSCLC. It will be performed on tumor specimens for patients who are potentially eligible for this study. Patients identified through the assay as intermediate or high-risk will be randomized to either adjuvant chemotherapy or observation.

Locations

Country	Name	City	State
France	CHU d'Angers Service Pneumologie	Angers
France	Centre Hospitalier de la Côte Basque	Bayonne
France	CHRU Besançon- Hôpital J. MINJOZ	Besancon
France	Polyclinique Bordeaux Nord	Bordeaux	Cedex
France	Hôpital APHP Ambroise Paré	Boulogne
France	Hia Percy	Clamart
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Centre Hospitalier Départemental Vendée	La Roche-sur-yon
France	Hôpital Privé Jean Mermoz	Lyon
France	Hôpital Europeen	Marseille
France	Hôpital Nord	Marseille
France	Groupe Hospitalier Région de Mulhouse Sud -Alsace	Mulhouse
France	Centre Hospitalier Universitaire de Nîmes	Nîmes
France	Hôpital Bichat	Paris
France	Hôpital Cochin	Paris
France	Hôpital Paris Saint Joseph	Paris
France	Hôpital Tenon	Paris
France	Hôpital Haut-Lévèque (Bordeaux - CHU)	Pessac
France	Chu de Poitiers	Poitiers
France	Hôpital Charles Nicolle	Rouen	Cedex
France	Toulon HIA Sainte Anne-	Toulon	Cedex 9
France	Hôpital Larrey	Toulouse
France	CHRU de Tours	Tours
France	Gustave Roussy	Villejuif
Germany	Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH - Universitätsklinik -	Essen
Germany	München-Gauting	Gauting
Germany	Niels-Stensen-Kliniken	Georgsmarienhütte
Germany	Lung Clinic Grosshansdorf-Department of Thoracic Oncology	Grosshansdorf
Germany	Köln-Merheim	Köln
Germany	Pius-Hospital Oldenburg Medizinischer Campus Universität Oldenburg	Oldenburg
United States	Sarah Cannon- Messino Cancer Center	Asheville	North Carolina
United States	Sarah Cannon- FCS South	Fort Myers	Florida
United States	St. Francis Cancer Center	Greenville	South Carolina
United States	Mercy Hospital Joplin Missouri	Joplin	Missouri
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Leonard Cancer Institute	Mission Viejo	California
United States	Sarah Cannon Tennessee Oncology	Nashville	Tennessee
United States	Hackensack Meridian Health	Neptune	New Jersey
United States	Mercy Oncology Research Oklahoma City	Oklahoma City	Oklahoma
United States	Baptist Health Paducah	Paducah	Kentucky
United States	Allegheny Health Network Research Institute	Pittsburgh	Pennsylvania
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Mercy Oncology Research St. Louis	Saint Louis	Missouri
United States	Sarah Cannon- FCS North	Saint Petersburg	Florida
United States	Providence Medical Foundation Santa Rosa	Santa Rosa	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Sarah Cannon- FCS Panhandle	Tallahassee	Florida
United States	Sarah Cannon- FCS East	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Razor Genomics	Encore Clinical

Countries where clinical trial is conducted

United States,  France,  Germany, 

References & Publications (3)

Kratz JR, He J, Van Den Eeden SK, Zhu ZH, Gao W, Pham PT, Mulvihill MS, Ziaei F, Zhang H, Su B, Zhi X, Quesenberry CP, Habel LA, Deng Q, Wang Z, Zhou J, Li H, Huang MC, Yeh CC, Segal MR, Ray MR, Jones KD, Raz DJ, Xu Z, Jahan TM, Berryman D, He B, Mann MJ, Jablons DM. A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies. Lancet. 2012 Mar 3;379(9818):823-32. doi: 10.1016/S0140-6736(11)61941-7. Epub 2012 Jan 27. — View Citation

Kratz JR, Van den Eeden SK, He J, Jablons DM, Mann MJ. A prognostic assay to identify patients at high risk of mortality despite small, node-negative lung tumors. JAMA. 2012 Oct 24;308(16):1629-31. doi: 10.1001/jama.2012.13551. No abstract available. — View Citation

Woodard GA, Wang SX, Kratz JR, Zoon-Besselink CT, Chiang CY, Gubens MA, Jahan TM, Blakely CM, Jones KD, Mann MJ, Jablons DM. Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage, Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2018 Jan;19(1):58-64. doi: 10.1016/j.cllc.2017.05.015. Epub 2017 May 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival	To compare Disease Free Survival in patients with resected, stage I or IIA non-squamous NSCLC found to be at intermediate or high risk by the 14-Gene Prognostic Assay randomized to either observation or adjuvant therapy with 4 cycles of a platinum-based doublet.	5 years
Secondary	Overall Survival	To compare Overall Survival in patients randomized to each study arm. To further document the previously verified separation of the survival curves among high and low risk patients identified by the 14-Gene Prognostic Assay in this prospective cohort of stage I or IIA non-squamous NSCLC.	5 years