Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Squamous, Adjuvant Chemotherapy, IFCT
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.
Interventions
DRUGAdjuvant 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.
OTHERRadiographic 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.
OTHER14-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.
Sponsors
Razor Genomics
Encore Clinical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Results of 14-Gene prognostic assay will not be revealed to the patient. Low risk patients will be observed, intermediate and high risk patients will be randomized to observation or four cycles of a platinum-based doublet therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 5 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. |
Countries
France, Germany, United States
Contacts
PRINCIPAL_INVESTIGATORDavid R Spigel, MD
Sarah Cannon, The Cancer Institute of HCA Healthcare
Outcome results
None listed