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)

NCT01817192 | Active Not Recruiting DMC

• 2 other identifiers: EC-120888IFCT-2002
• Study Type: interventional
• Target: 420
• Locations: 3 countries
• Sites: 49

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Squamous; Adjuvant Chemotherapy; IFCT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Overall Survival

  5 years

Study Arms (2)

Observation

ACTIVE COMPARATOR

Post-operative observation of Stage I or Stage IIA non squamous non-small cell lunger cancer with Radiographic Surveillance is a current standard of care. Patients identified as low risk will be observation. Those patients identified as intermediate or high-risk by the 14-Gene Prognostic Assay will be randomized either to this arm or the Adjuvant Chemotherapy Arm.

Other: Radiographic surveillance; Other: 14-Gene Prognostic Assay

Adjuvant Chemotherapy

ACTIVE COMPARATOR

Adjuvant Chemotherapy is a current standard of care for intermediate or high-risk Stage I or Stage IIA non-squamous non-small cell lung cancer. Patients identified as intermediate or high-risk by the 14-Gene Prognostic Assay will be randomized either to this arm or the Observation Arm.

Drug: Adjuvant Chemotherapy; Other: 14-Gene Prognostic Assay

Interventions

Adjuvant Chemotherapy DRUG

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.

Adjuvant Chemotherapy

Radiographic surveillance OTHER

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.

Observation

14-Gene Prognostic Assay OTHER

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.

Adjuvant Chemotherapy; Observation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Razor Genomics: lead
• Encore Clinical: collaborator

Study Sites (49)

Leonard Cancer Institute

Mission Viejo, California, 92961, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Providence Medical Foundation Santa Rosa

Santa Rosa, California, 95403, United States

Location

Sarah Cannon- FCS South

Fort Meyers, Florida, 33916, United States

Location

Sarah Cannon- FCS North

Petersburg, Florida, 33705, United States

Location

Sarah Cannon- FCS Panhandle

Tallahassee, Florida, 32308, United States

Location

Sarah Cannon- FCS East

West Palm Beach, Florida, 33401, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Baptist Health Louisville

Louisville, Kentucky, 40207, United States

Location

Mercy Hospital Joplin Missouri

Joplin, Missouri, 65804, United States

Location

Mercy Oncology Research St. Louis

St Louis, Missouri, 63141, United States

Location

Hackensack Meridian Health

Neptune City, New Jersey, 07753, United States

Location

Sarah Cannon- Messino Cancer Center

Asheville, North Carolina, 28803, United States

Location

Mercy Oncology Research Oklahoma City

Oklahoma City, Oklahoma, 73120, United States

Location

Allegheny Health Network Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

St. Francis Cancer Center

Greenville, South Carolina, 29607, United States

Location

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Polyclinique Bordeaux Nord

Bordeaux, Cedex, France

Location

Hôpital Charles Nicolle

Rouen, Cedex, 76031, France

Location

CHU d'Angers Service Pneumologie

Angers, 49033, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 33077, France

Location

CHRU Besançon- Hôpital J. MINJOZ

Besançon, 25000, France

Location

Hôpital APHP Ambroise Paré

Boulogne, 92104, France

Location

Hia Percy

Clamart, 92141, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94000, France

Location

Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, 85925, France

Location

Hôpital Privé Jean Mermoz

Lyon, 69008, France

Location

Hôpital Europeen

Marseille, 13291, France

Location

Hôpital Nord

Marseille, 13915, France

Location

Groupe Hospitalier Région de Mulhouse Sud -Alsace

Mulhouse, 680100, France

Location

Centre Hospitalier Universitaire de Nîmes

Nîmes, 30029, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Tenon

Paris, 75020, France

Location

Hôpital Paris Saint Joseph

Paris, 75674, France

Location

Hôpital Bichat

Paris, 75877, France

Location

Hôpital Haut-Lévèque (Bordeaux - CHU)

Pessac, 33604, France

Location

Chu de Poitiers

Poitiers, 86021, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

CHRU de Tours

Tours, 37044, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Köln-Merheim

Cologne, 51109, Germany

Location

München-Gauting

Gauting, 82131, Germany

Location

Niels-Stensen-Kliniken

Georgsmarienhütte, Germany

Location

Lung Clinic Grosshansdorf-Department of Thoracic Oncology

Großhansdorf, 22927, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

University Medical Center Schleswig-Holstein

Lübeck, Germany

Location

University Hospital of Munich

München, 80336, Germany

Location

Pius-Hospital Oldenburg Medizinischer Campus Universität Oldenburg

Oldenburg, Germany

Location

Related Publications (4)

• 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.

  PMID: 22285053 BACKGROUND

• 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.

  PMID: 28645632 BACKGROUND

• 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.

  PMID: 23093159 BACKGROUND

• Spigel DR, Westeel V, Anderson IC, Greillier L, Guisier F, Bylicki O, Badin FB, Rousseau-Bussac G, Deldycke C, Griesinger F, Bograd A, Zhong W, Le Treut J, Van Hulst S, Gandara DR, Reck M, Hoffknecht P, Gubens MA, Crowley J, von der Leyen H, Woodard GA, Jablons DM, Kratz JR, Mann MJ; AIM-HIGH investigators. Adjuvant chemotherapy for stage IA-IIA non-squamous, non-small-cell lung cancer identified as molecular high-risk by a 14-gene expression profile (AIM-HIGH): an international, randomised, phase 3 trial. Lancet Respir Med. 2025 Oct;13(10):887-896. doi: 10.1016/S2213-2600(25)00213-9. Epub 2025 Jun 24.

  PMID: 40578381 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• David R Spigel, MD

  Sarah Cannon, The Cancer Institute of HCA Healthcare

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Results of 14-Gene prognostic assay will not be revealed to the patient. Low risk patients will be observed, intermediate and high risk patients will be randomized to observation or four cycles of a platinum-based doublet therapy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2013
• First Posted: March 25, 2013
• Study Start: September 11, 2020
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 15, 2027
• Last Updated: April 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (23); US (18); DE (8)