Chemotherapy and Radiation Therapy with or without Panitumumab in Treating Patients with Stage IIIA Non-Small Cell Lung Cancer (Cetuximab Closed as of 05/14/10)

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Treatment18 and overRTOG 0839
NCI-2011-01970, CDR0000654690, NCT00979212

Trial Description

Summary

This randomized phase II trial studies how well chemotherapy and radiation therapy with or without panitumumab work in treating patients with stage IIIA non-small cell lung cancer. (cetuximab closed as of 05/14/10) Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Panitumumab may delay or prevent tumor growth by blocking certain cellular chemical pathways that lead to tumor development and growth. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without panitumumab in treating patients with non-small cell lung cancer. (cetuximab closed as of 05/14/10)

Further Study Information

PRIMARY OBJECTIVES:

I. Mediastinal nodal clearance following completion of induction chemoradiation +/- panitumumab. (cetuximab closed as of 05/14/10)

SECONDARY OBJECTIVES:

I. Overall survival.

II. Patterns of first failure.

III. Acute and late adverse events.

IV. Surgical morbidities among resectable patients at reassessment.

V. Correlation between biomarkers (including at least epidermal growth factor receptor [EGFR] and rat sarcoma [ras] mutation status) in pre- and post-therapy and outcomes (mediastinal nodal clearance and overall survival).

VI. Evaluation of the prognostic value of plasma osteopontin and micro ribonucleic acid (RNA) for overall survival.

VII. Assess the ability of positron emission tomography (PET)/computed tomography (CT) scan re-staging to predict outcome.

VIII. Estimate response rate.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive induction therapy comprising paclitaxel intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo intensity-modulated radiotherapy (IMRT) or 3-dimensional (D)-conformal radiotherapy (CRT) once daily (QD) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning approximately 6-12 weeks later, patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 22.

ARM II: Patients receive induction therapy comprising panitumumab IV over 1 hour on days 1, 8, 15, 22, 29, and 36 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 8, 15, 22, 29, and 36. Patients also undergo IMRT or 3D-CRT QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning approximately 6-12 weeks later, patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 22. (cetuximab closed as of 05/14/10)

In both arms, patients with resectable disease and no disease progression may proceed to surgery (thoracotomy, lobectomy, or pneumonectomy) approximately 4-6 weeks after completion of induction therapy. After surgery, patients proceed to consolidation therapy.

After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Eligibility Criteria

Inclusion Criteria:

Hemoglobin >= 10.0 g/dL (note: the use of transfusion or other intervention to achieve Hgb >= 10.0 g/dl is acceptable)

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 (EBUS-TBNA)

Thoracotomy

Video-assisted thoracoscopy

Transbronchial needle biopsy by Wang technique (TBNA)

Fine needle aspiration under CT guidance

Note: Demonstration of N2 status DOES NOT require sampling of all potentially positive nodes; it is adequate to document any N2 node as positive at the time of registration; for left sided lesions, the following nodal levels should be biopsied: 2L, 4L, 2R, 4R and 7 or stations 5 and 6 whenever possible to rule out microscopically involved lymph nodes; for right sided lesions levels 2R, 4R, 2L, 4L and 7 should be sampled whenever possible to rule out microscopically involved lymph nodes; investigators are strongly encouraged to biopsy multiple stations of mediastinal lymph nodes at the time of invasive staging in addition to those nodes that are abnormal on PET/CT or CT scan; PET/CT positivity in the ipsilateral mediastinal lymph nodes will not be sufficient to establish N2 nodal status; 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 aortopulmonary (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, 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

If the procedures to document N2 eligibility were done at a non-member facility, the patient is still eligible if the institution principal investigator (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

Electrocardiogram (EKG) within 8 weeks of registration

Measurable disease as determined by contrast-enhanced CT scan with primary lung tumor distinct from mediastinal lymph nodes

Absolute neutrophil count (ANC) >= 1,500/mm^3

Serum magnesium within normal range (patients may receive magnesium supplementation to achieve normal levels)

For women of childbearing potential, a negative serum pregnancy test within 2 weeks of registration

Serum albumin > 3.0 g/dL

Pathologically proven diagnosis of stage IIIA (T1-T3) (American Joint Committee on Cancer [AJCC] Staging, 7th edition) 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

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

Total bilirubin =< 1.5 x upper limit of normal (ULN)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN

Alkaline phosphatase =< 2.5 x ULN

Adequate pulmonary function based on the following pulmonary function tests done within 8 weeks of registration:

Forced expiratory volume (FEV)1 at least 2.0 liters; if less than 2.0 liters, the predicted post-resection FEV1 must be at least 0.8 liters

Diffusion capacity should be >= 50% predicted

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 not otherwise specified [NOS]) within 12 weeks of registration; note: mixed small cell and non-small cell histologies are not eligible for this study

Creatinine clearance within 2 weeks of registration must be at least 60 ml/min

Zubrod performance status 0-1 within 8 weeks of registration

Platelet count >= 100,000/mm^3

Patient must provide study specific informed consent prior to study entry

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

Whole body fludeoxyglucose F 18 (FDG)-PET (or PET/CT) scan within 6 weeks of registration

A magnetic resonance imaging (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

Exclusion Criteria:

Severe, active co-morbidity, including any of the following:

Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction (within the past 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 Centers for Disease Control and Prevention (CDC) definition or patients known to be human immunodeficiency virus (HIV) positive; note, however, that HIV testing is not required for entry into this protocol

Prior systemic chemotherapy or biological therapy (including erlotinib [erlotinib hydrochloride) or similar agents) for the study cancer; note that prior chemotherapy for a different cancer allowable

Unintentional weight loss >= 5% of body weight within the past 6 months

Prior severe infusion reaction to a monoclonal antibody

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

Prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway

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)

Pre-existing peripheral motor or sensory neuropathy >= grade 2

Prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields

Palpable lymph nodes present in the supraclavicular areas or higher in the neck, unless proven to be benign on fine needle aspiration or biopsy

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

NRG Oncology

  • National Cancer Institute
Martin J. Edelman, Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00979212

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.