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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)

Not Applicable
Active, not recruiting
Conditions
Non-Small Cell Lung Cancer
Interventions
Other: Radiographic surveillance
Drug: Adjuvant Chemotherapy
Other: 14-Gene Prognostic Assay
Registration Number
NCT01817192
Lead Sponsor
Razor Genomics
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
420
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ObservationRadiographic surveillancePost-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.
Observation14-Gene Prognostic AssayPost-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.
Adjuvant ChemotherapyAdjuvant ChemotherapyAdjuvant 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.
Adjuvant Chemotherapy14-Gene Prognostic AssayAdjuvant 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.
Primary Outcome Measures
NameTimeMethod
Disease-Free Survival5 years

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.

Secondary Outcome Measures
NameTimeMethod
Overall Survival5 years

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.

Trial Locations

Locations (49)

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

München-Gauting

🇩🇪

Gauting, Germany

Niels-Stensen-Kliniken

🇩🇪

Georgsmarienhütte, Germany

Hôpital APHP Ambroise Paré

🇫🇷

Boulogne, France

Hia Percy

🇫🇷

Clamart, France

Centre Hospitalier Intercommunal de Créteil

🇫🇷

Créteil, France

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

🇺🇸

Ft 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, 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

🇫🇷

Besancon, France

Lung Clinic Grosshansdorf-Department of Thoracic Oncology

🇩🇪

Grosshansdorf, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Germany

Köln-Merheim

🇩🇪

Köln, Germany

University Medical Center Schleswig-Holstein

🇩🇪

Lübeck, Germany

University Hospital of Munich

🇩🇪

München, Germany

Pius-Hospital Oldenburg Medizinischer Campus Universität Oldenburg

🇩🇪

Oldenburg, Germany

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