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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Adjuvant Chemotherapy
* Other: Radiographic surveillance
* Other: 14-Gene Prognostic Assay


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Observation<br>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<br>* 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.<br>Other: 14-Gene Prognostic Assay<br>* 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.<br>|
| Active Comparator: Adjuvant Chemotherapy<br>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<br>* 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.<br>Other: 14-Gene Prognostic Assay<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Squamous, Adjuvant Chemotherapy, IFCT