Details
Description
Inclusion Criteria
Exclusion Criteria
Details
Title Randomized Phase II Study of Pre-Operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed By Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer
IRB RTOG0839
CC CC00137
Hospital Main Campus, Strongsville
Stage Stage 3A
Phase Phase 2
Disease Lung
Drug Panitumumab
Description
Primary Objective- Mediastinal nodal clearance following completion of induction chemoradiation +/- panitumumab
- Overall survival;
- Patterns of first failure;
- Acute and late adverse events;
- Surgical morbidities among resectable patients at reassessment;
- Correlation between biomarkers (including at least EGFR and ras mutation status) in pre- and post-therapy and outcomes (mediastinal nodal clearance and overall survival);
- Evaluation of the prognostic value of plasma osteopontin and microRNA for overall survival;
- Assess the ability of PET/CT scan re-staging to predict outcome;
- Estimate response rate.
Inclusion Criteria
- Pathologically proven diagnosis of Stage IIIA (T1-T3) [AJCC Staging, 7th edition; see Appendix II] with a single primary lung parenchymal lesion and ipsilateral positive mediastinal nodes within 12 weeks of registration; Note: The primary tumor does not require tissue diagnosis; documentation of non-small cell carcinoma may originate from the mediastinal node biopsy or aspiration.
- Histologic proof of non-small cell histology (adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer NOS) within 12 weeks of registration; note: mixed small cell and non-small cell histologies are not eligible for this study.
- Measurable disease as determined by contrast-enhanced CT scan with the primary lung tumor distinct from mediastinal lymph nodes;
- Positive ipsilateral mediastinal node or nodes (N2), with or without positive ipsilateral hilar nodes (N1); N2 nodes must be separate from primary tumor by either CT scan or surgical exploration, and the maximum nodal diameter of involved N2 nodes cannot exceed 3.0 cm.
- N2 status must be pathologically confirmed to be positive within 12 weeks prior to registration by one of the following:
- mediastinoscopy;
- mediastinotomy (Chamberlain procedure);
- transesophageal needle biopsy using endoscopic ultrasound (EUS-TBNA);
- endobronchial ultrasound biopsy using endoscopic ultrasound guidance (EBUSTBNA);
- thoracotomy;
- video-assisted thoracoscopy;
- transbronchial needle biopsy by Wang technique (TBNA);
- fine needle aspiration under CT guidance.
- Ipsilateral mediastinal lymph nodes associated with right sided tumors must be biopsied.
- The mediastinal nodal biopsy or aspiration can only be omitted in the special circumstance in which ALL of the following are true:
- The tumor is left sided;
- Paralyzed left true vocal cord documented by bronchoscopy or indirect laryngoscopy; Note: bronchoscopy is not required but is at the discretion of the patient's surgeon. It is recommended in patients who have central tumors or disease near the carina or in another position that may impact resectability, or to document paralyzed recurrent laryngeal nerve, in cases of AP nodal involvement.
- Nodes visible in the AP (level 5) region on CT scan;
- Distinct primary tumor separate from the nodes is visible on CT scan;
- Histologic (biopsy) or cytologic (needle aspiration or sputum) proof of non-small cell histology from the primary tumor.
- Regardless of method of documentation of N2 disease (see Section 3.1.3), the following must be documented:
- From the Operative and Pathology reports, all mediastinal nodes shown to be both positive and negative (including contralateral nodes) must be designated on the I1 form according to the Lymph Node Map in Appendix IV.
- If the procedures to document N2 eligibility were done at a non-member facility, the patient is still eligible if the institution PI reviews the outside pathology slides and report with the institution's pathologist in conjunction with the outside operative report, and generates a report that verifies the original diagnosis and lymph node mapping, as consistent with the staging requirements of the protocol.
- If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (incurable M1a disease):
- When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
- Exudative pleural effusions are excluded, regardless of cytology;
- Effusions that are minimal (i.e. not visible under ultrasound guidance) that are too small to safely tap are eligible.
- Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- History/physical examination, including a neurological assessment, within 8 weeks of registration;
- Evaluation by a thoracic surgeon within 4 weeks of registration; the patient must be deemed potentially operable and resectable to be eligible for the study. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Resectable is defined as an R0 resection possible either by lobectomy or pneumonectomy at the time of initial evaluation.
- Whole body FDG-PET (or PET/CT) scan within 6 weeks of registration; Note: PET/CT data will be used for the analysis of a secondary endpoint (Section 2.2.7). To be included in this analysis, the patient's PET/CT studies must be performed with a dedicated BGO, LSO, or GSO PET or PET/CT scanner. PET/CT scanners with sodium iodide (Nal) detectors are not acceptable. PET/CT DICOM images, diagnostic reports, and assessment forms must be submitted as described in Section 12.1. If an additional treatment planning FDG PET/CT (in the treatment position, see Section 6.3.3) is performed after the initial diagnostic staging PET/CT, the most recent scan data prior to initiation of treatment should be submitted as described. If the baseline PET/CT study is performed at the treating institution (or its affiliated PET facility), it is recommended but not required that the reassessment PET/CT scan (see Section 8.1.2) will be performed at the same site. Note: National Cancer Institute recommendations regarding performance of the scans should be followed as closely as possible (Shankar 2006).
- An MRI with contrast of the brain (or CT scan with contrast of brain, if an MRI is medically contraindicated) within 5 weeks of registration;
- A CT scan with contrast of the lungs and upper abdomen to complete T and N staging and exclude other ipsilateral or contralateral parenchymal lesions and liver or adrenal metastases within 5 weeks of registration; note: a whole body FDG-PET/CT scan within 6 weeks of registration will satisfy this criterion. An additional chest x-ray is optional.li>
- Zubrod Performance Status 0-1 within 8 weeks of registration;
- Age ≥ 18;
- EKG within 8 weeks of registration;
- Adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm³ based on a CBC/differential obtained within 2 weeks prior to registration;
- Platelets ≥ 100,000 cells/mm³ based on a CBC/differential obtained within 2 weeks prior to registration;
- Hemoglobin ≥ 10.0 g/dl based on a CBC/differential obtained within 2 weeks prior to registration (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable.);
- Adequate renal function, defined as follows: creatinine clearance within 2 weeks of registration must be at least 60 ml/min; this may be measured or calculated according to the following formula: (140-age) x (body weight in kg) x 0.85 for females / 72 x serum creatinine
- Adequate hepatic function, defined as follows: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution within 2 weeks of registration;
- Serum albumin > 3.0 g/dl within 2 weeks of registration;
- Serum magnesium within normal range within 2 weeks of registration; patients may receive magnesium supplementation to achieve normal levels.
- For women of childbearing potential, a negative serum pregnancy test within 2 weeks of registration;
- Adequate pulmonary function based on the following pulmonary function tests done within 8 weeks of registration:
- FEV1 at least 2.0 liters; if less than 2.0 liters, the predicted post-resection FEV1 must be at least 0.8 liters based on the following formula using the quantitative V/Q scan: Predicted post-resection FEV1=FEV1 x % perfusion to the residual, unresected lung or segment counting (predicted post-resection FEV1 = preopFEV1 x (# segments remaining/total # of segments).
- Diffusion capacity should be ≥ 50% predicted;
- Patient must provide study specific informed consent prior to study entry.
Exclusion Criteria
- Palpable lymph nodes present in the supraclavicular areas or higher in the neck, unless proven to be benign on fine needle aspiration or biopsy;
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
- Prior systemic chemotherapy or biologic agent (including erlotinib or similar agents) for the study cancer; note that prior chemotherapy for a different cancer is allowable.
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
- Severe, active co-morbidity, defined as follows:
- Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction (< 50%);
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 4 weeks of registration;
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
- Patients with acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition or patients known to be HIV positive; note, however, that HIV testing is not required for entry into this protocol. The need to exclude these patients from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.
- Unintentional weight loss ≥ 5% of body weight over the preceding 6 months;
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during the trial and for 6 months after completion of treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
- Prior therapy that specifically and directly targets the EGFR pathway;
- Prior severe infusion reaction to a monoclonal antibody;
- Pre-existing ≥ grade 2 peripheral motor or sensory neuropathy.
