Clinical trial NCT01817192: Adjuvant Chemotherapy in Patients With Intermediate or High Risk Stage I or Stage IIA Non-squamous Non-Small Cell Lung Cancer: AIM-HIGH (Adjuvant Intervention in Molecular High Risk Patients)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Squamous
Adjuvant Chemotherapy
IFCT
Lead sponsor: Encore Clinical
Sponsor class: OTHER
Collaborators: name: Encore Clinical
First posted: 2013-03-25
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Exclusion Criteria:

* Final pathologic diagnosis of pure squamous cell, pure small cell, or pure neuroendocrine histology, or any combination of only these three histologies
* Evidence of greater than stage IIA pathologic staging
* Evidence of incomplete resection
* Pregnant or lactating women
* Unwilling to use an effective means of contraception
* Active infection, either systemic or at site of primary resection
* Systemic chemotherapy or anti-cancer agent within 5 years prior to enrollment
* Radiotherapy to the chest in the immediate pre- or post- operative period
* Malignancies other than the current NSCLC within 5 years prior to randomization, except for adequately treated CIS of the cervix, non-melanoma skin cancer, localized prostate cancer treated locally, ductal carcinoma in situ treated surgically
* Treatment with any investigational drug or participation in another clinical trial within 28 days prior to enrollment
* Known hypersensitivity to study treatment agents
* Evidence of any other disease including infection that contraindicates the use of systemic cytotoxic chemotherapy or puts the patient at high risk for treatment-related complications
* Wound dehiscence or infection

Primary outcomes:
measure: Disease-Free Survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Mission Viejo
country: United States
facility: Leonard Cancer Institute
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation Santa Rosa
state: California
city: Ft Meyers
country: United States
facility: Sarah Cannon- FCS South
state: Florida
city: Petersburg
country: United States
facility: Sarah Cannon- FCS North
state: Florida
city: Tallahassee,
country: United States
facility: Sarah Cannon- FCS Panhandle
state: Florida
city: West Palm Beach
country: United States
facility: Sarah Cannon- FCS East
state: Florida
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Joplin
country: United States
facility: Mercy Hospital Joplin Missouri
state: Missouri
city: St Louis
country: United States
facility: Mercy Oncology Research St. Louis
state: Missouri
city: Neptune
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: Asheville
country: United States
facility: Sarah Cannon- Messino Cancer Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Mercy Oncology Research Oklahoma City
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allegheny Health Network Research Institute
state: Pennsylvania
city: Greenville
country: United States
facility: St. Francis Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Tennessee Oncology
state: Tennessee
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord
state: Cedex
city: Rouen
country: France
facility: Hôpital Charles Nicolle
state: Cedex
city: Angers
country: France
facility: CHU d'Angers Service Pneumologie
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Besancon
country: France
facility: CHRU Besançon- Hôpital J. MINJOZ
city: Boulogne
country: France
facility: Hôpital APHP Ambroise Paré
city: Clamart
country: France
facility: Hia Percy
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: La Roche-sur-yon
country: France
facility: Centre Hospitalier Départemental Vendée
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Hôpital Europeen
city: Marseille
country: France
facility: Hôpital Nord
city: Mulhouse
country: France
facility: Groupe Hospitalier Région de Mulhouse Sud -Alsace
city: Nîmes
country: France
facility: Centre Hospitalier Universitaire de Nîmes
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Hôpital Paris Saint Joseph
city: Paris
country: France
facility: Hôpital Bichat
city: Pessac
country: France
facility: Hôpital Haut-Lévèque (Bordeaux - CHU)
city: Poitiers
country: France
facility: Chu de Poitiers
city: Toulouse
country: France
facility: Hôpital Larrey
city: Tours
country: France
facility: CHRU de Tours
city: Villejuif
country: France
facility: Gustave Roussy
city: Gauting
country: Germany
facility: München-Gauting
city: Georgsmarienhütte
country: Germany
facility: Niels-Stensen-Kliniken
city: Grosshansdorf
country: Germany
facility: Lung Clinic Grosshansdorf-Department of Thoracic Oncology
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Köln
country: Germany
facility: Köln-Merheim
city: Lübeck
country: Germany
facility: University Medical Center Schleswig-Holstein
city: München
country: Germany
facility: University Hospital of Munich
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg Medizinischer Campus Universität Oldenburg
Study officials:
affiliation: Sarah Cannon, The Cancer Institute of HCA Healthcare
name: David R Spigel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.