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)

NCT ID: NCT01817192

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 420 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-11
• Study Completion Date: 2027-05-15

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Observation

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.

Group Type: ACTIVE_COMPARATOR

Radiographic surveillance

Intervention Type: 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.

14-Gene Prognostic Assay

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Adjuvant Chemotherapy

Intervention Type: 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.

14-Gene Prognostic Assay

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Encore Clinical

OTHER

Sponsor Role: collaborator

Razor Genomics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David R Spigel, MD

Role: PRINCIPAL_INVESTIGATOR

Sarah Cannon, The Cancer Institute of HCA Healthcare

Locations

Leonard Cancer Institute

Mission Viejo, California, United States

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Providence Medical Foundation Santa Rosa

Santa Rosa, California, United States

Sarah Cannon- FCS South

Fort Meyers, Florida, United States

Sarah Cannon- FCS North

Petersburg, Florida, United States

Sarah Cannon- FCS Panhandle

Tallahassee, Florida, United States

Sarah Cannon- FCS East

West Palm Beach, Florida, United States

Baptist Health Lexington

Lexington, Kentucky, United States

Baptist Health Louisville

Louisville, Kentucky, United States

Mercy Hospital Joplin Missouri

Joplin, Missouri, United States

Mercy Oncology Research St. Louis

St Louis, Missouri, United States

Hackensack Meridian Health

Neptune City, New Jersey, United States

Sarah Cannon- Messino Cancer Center

Asheville, North Carolina, United States

Mercy Oncology Research Oklahoma City

Oklahoma City, Oklahoma, United States

Allegheny Health Network Research Institute

Pittsburgh, Pennsylvania, United States

St. Francis Cancer Center

Greenville, South Carolina, United States

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, United States

Swedish Cancer Institute

Seattle, Washington, United States

Polyclinique Bordeaux Nord

Bordeaux, Cedex, France

Hôpital Charles Nicolle

Rouen, Cedex, France

CHU d'Angers Service Pneumologie

Angers, , France

Centre Hospitalier de la Côte Basque

Bayonne, , France

CHRU Besançon- Hôpital J. MINJOZ

Besançon, , 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 Cochin

Paris, , France

Hôpital Tenon

Paris, , France

Hôpital Paris Saint Joseph

Paris, , France

Hôpital Bichat

Paris, , France

Hôpital Haut-Lévèque (Bordeaux - CHU)

Pessac, , France

Chu de Poitiers

Poitiers, , France

Hôpital Larrey

Toulouse, , France

CHRU de Tours

Tours, , France

Gustave Roussy

Villejuif, , France

Köln-Merheim

Cologne, , Germany

München-Gauting

Gauting, , Germany

Niels-Stensen-Kliniken

Georgsmarienhütte, , Germany

Lung Clinic Grosshansdorf-Department of Thoracic Oncology

Großhansdorf, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

University Medical Center Schleswig-Holstein

Lübeck, , Germany

University Hospital of Munich

München, , Germany

Pius-Hospital Oldenburg Medizinischer Campus Universität Oldenburg

Oldenburg, , Germany

Countries

United States; France; Germany

References

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.

Reference Type: BACKGROUND

PMID: 22285053 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28645632 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23093159 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40578381 (View on PubMed)

Other Identifiers

IFCT-2002

Identifier Type: OTHER

Identifier Source: secondary_id

EC-120888

Identifier Type: -

Identifier Source: org_study_id