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
Overview
- Phase
- Not Applicable
- Intervention
- Radiographic surveillance
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Razor Genomics
- Enrollment
- 420
- Locations
- 49
- Primary Endpoint
- Disease-Free Survival
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
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
Arms & Interventions
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.
Intervention: Radiographic surveillance
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.
Intervention: 14-Gene Prognostic Assay
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.
Intervention: Adjuvant Chemotherapy
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.
Intervention: 14-Gene Prognostic Assay
Outcomes
Primary Outcomes
Disease-Free Survival
Time Frame: 5 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 Outcomes
- Overall Survival(5 years)