predictive assay for decision making in adjuvant therapy

Conditions: Carcinoma, Non-Small-Cell Lung

Summary: prospective registrational trial to define real world outcomes of patients with completely resected stage i or iia (tumor \< or = 5cm, node negative) non-squamous non-small lung cancer (nsclc) identified as high, intermediate, or low risk by a 14-gene prognostic assay determarx being considered for adjuvant platinum-based chemotherapy or other adjuvant therapy versus observation

this is a prospective, non-randomized, 2 arm, multi-center study in patients with histologically documented non-squamous nsclc who have undergone complete resection (r0) of the primary tumor with pathologically stage i or iia disease. routine paraffin-embedded tumor specimens from completely resected (r0) stage i or iia patients with non-squamous nsclc will undergo testing with the determarx 14-gene prognostic assay and will be designated as high, intermediate or low risk by the assay. the physician and patient will determine the best treatment course and will be assigned to treatment arm based on decision of adjuvant therapy or observation: 1. adjuvant treatment with a standard nsclc platin-based doublet, 4 cycle (21-day) regimen of the investigator's choice (arm 1) or other adjuvant therapy (arm 1a) which can include combination of chemotherapy and targeted therapy, immunotherapy or other. 2. observation (arm 2) all patients will be observed for progression free survival and overall survival to the end of study or death, whichever occurs first. all patients will be observed for disease free survival and overall survival to the end of study or death, whichever occurs first

Eligibility criteria:
inclusion criteria: 1. written informed consent using the appropriate approved institutional review board (irb) approved consent. 2. age ≥ 18 years 3. able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy and likely compliance with follow-up for anticipated length of study (18 months from randomization). 4. adequate tissue sample, paraffin block with tumor occupying at least 25% of the tissue surface area, for the 14 -gene prognostic assay, determarx 5. histologically documented completely resected (r0) stage i or iia non-squamous nsclc per 8th edition, tnm staging system. mixed histology cases (adenosquamous), large cell, or adenocarcinoma not otherwise classified (nos) are eligible for the study, as long as they contain at least some component that is neither squamous cell, nor small cell nor neuroendocrine. eligible resections include lobectomy, bilobectomy, segmentectomy, sleeve lobectomy and pneumonectomy. resections via segmentectomy or wedge resection should be limited to patients with a peripheral tumor 2 cm or less with wide margins (\> 2 cm or \> the size of the nodule). complete resection must also be accompanied, at a minimum, by intra-operative systematic mediastinal lymph node sampling. systematic sampling is defined as removal of at least one representative lymph node each from levels 4 and 7 for a right-sided cancer and from levels 5 and/or 6 and 7 for left-sided cancers. complete mediastinal lymph node dissection (mlnd), however, is preferred, and is defined as resection of all lymph nodes at those same levels for right- and left-sided cancers. 6. ecog performance status 0-1 7. no prior anti-neoplastic (nsclc ) treatment in the pre-operative or post-operative setting (including chemotherapy, targeted therapy, immunotherapy, radiation, ablative procedures, etc.) exclusion criteria: 1. final pathologic diagnosis of pure squamous cell, pure small cell, or pure neuroendocrine histology, or any combination of only these three histological subtypes. 2. evidence of greater than stage iia pathologic staging 3. evidence of incomplete resection (r1) 4. prior systemic chemotherapy or anti-cancer agent for nsclc 5. any pre- or post-operative radiotherapy for the index tumor being considered for enrollment

Keywords: non-squamous non-small cell lung cancer