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)

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.


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