Clinical trial NCT00979212: Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
adenocarcinoma of the lung
adenosquamous cell lung cancer
bronchoalveolar cell lung cancer
large cell lung cancer
squamous cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-09-17
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy (CT), 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 (RT) uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. 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.

PURPOSE: This randomized phase II trial is studying chemotherapy and radiation therapy to see how well they work when given with or without panitumumab in treating patients with stage IIIA non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the mediastinal nodal clearance after completion of induction chemoradiotherapy with or without panitumumab in patients with stage IIIA non-small cell lung cancer.

Secondary

* Assess overall survival of these patients.
* Evaluate patterns of first failure in these patients.
* Determine the acute and late adverse events associated with these regimens.
* Assess surgical morbidities in patients with resectable disease at reassessment.
* Determine the correlation between pre- and post-treatment biomarkers (including epidermal growth factor receptor (EGFR) and ras mutation status) and outcomes (mediastinal nodal clearance and overall survival).
* Evaluate the prognostic value of plasma osteopontin and microRNA for overall survival.
* Assess the ability of FDG-PET/CT scan re-staging to predict outcome.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive induction therapy comprising paclitaxel 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 conformal radiotherapy (3D-CRT) once daily 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 21.
* 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 once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. 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 21.
* 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: DISEASE CHARACTERISTICS:

* Histologically confirmed\* non-small cell lung cancer (NSCLC), including any of the following histologies:

  * Adenocarcinoma
  * Adenosquamous
  * Large cell carcinoma
  * Squamous cell carcinoma
  * Non-lobar and non-diffuse bronchoalveolar cell carcinoma
  * NSCLC not otherwise specified NOTE: \*Documentation of NSCLC may originate from the mediastinal node biopsy or aspiration
* Stage IIIA (T1-T3) disease with a single primary lung parenchymal lesion AND 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
  * Maximum nodal diameter of involved N2 nodes cannot exceed 3.0 cm
  * N2 status must be pathologically confirmed to be positive by one of the following methods\*:

    * 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: \*PET positivity in the ipsilateral mediastinal lymph nodes is not sufficient to establish N2 nodal status
  * Ipsilateral mediastinal nodes associated with right-sided tumor must be biopsied unless all of the following are true:

    * Tumor is left sided
    * Paralyzed left true vocal cord documented by bronchoscopy or indirect laryngoscopy
    * Nodes visible in the anterior/posterior (level 5) region on CT scan
    * Distinct primary tumor separate from nodes visible on CT scan
    * Histologic (biopsy) or cytologic (needle aspiration or sputum) proof of non-small cell histology from the primary tumor
  * If lymph nodes in the contralateral mediastinum and neck are visible on contrast CT scan of the chest and are \> 1.0 cm in short axis or if contralateral involvement is suggested by PET scan, then the nodes must be confirmed to be negative
* Measurable disease as determined by contrast-enhanced CT scan

  * Primary lung tumor distinct from mediastinal lymph nodes
* 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.
* No palpable lymph nodes in the supraclavicular areas or higher in the neck, unless proven to be benign by fine-needle aspiration or biopsy
* No distant metastases

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-1
* Absolute neutrophil count (ANC) ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 10.0 g/dL (transfusion allowed)
* Creatinine clearance ≥ 60 mL/min
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* Serum albumin \> 3.0 g/dL
* Serum magnesium normal (supplementation allowed)
* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after completion of treatment
* Forced expiratory volume at one second (FEV1) ≥ 2.0 L OR predicted post-resection FEV1 ≥ 0.8 L
* Diffusion capacity ≥ 50% predicted
* No other invasive malignancy within the past 3 years, except nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix
* No severe, active co-morbidity, including any of the following:

  * Current uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within the past 6 months, uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction (\<50%)
  * Acute bacterial or fungal infection requiring IV antibiotics
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or that would preclude study therapy within the past 4 weeks
  * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  * AIDS or known HIV positivity
* No unintentional weight loss ≥ 5% of body weight within the past 6 months
* No prior severe infusion reaction to a monoclonal antibody
* No pre-existing peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

* No prior systemic chemotherapy or biological therapy (including erlotinib hydrochloride or similar agents) for the study cancer

  * Prior chemotherapy for a different cancer allowed
* No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
* No prior therapy that specifically and directly targets the EGFR pathway

Primary outcomes:
measure: Mediastinal Nodal Clearance After Completion of Induction Chemoradiotherapy With or Without Panitumumab.
timeFrame: From date of randomization to time of protocol surgery, approximately 12 weeks.
Secondary outcomes:
measure: Overall Survival
timeFrame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study
measure: Patterns of First Failure
timeFrame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
measure: Percentage of Patients With Grade 3 or Higher Acute and Late Adverse Events
timeFrame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
measure: Surgical Morbidities in Patients With Resectable Disease at Reassessment
timeFrame: From date of surgery to 30 days following surgery.
measure: Ability of FDG-PET/CT Scan Data to Predict Outcome
timeFrame: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
measure: Response Rate
timeFrame: From date of randomization to time of protocol surgery, approximately 12 weeks.
Other outcomes:
Locations:
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan Medical Center
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Towson
country: United States
facility: Cancer Institute at St. Joseph Medical Center
state: Maryland
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Hanover
country: United States
facility: Cherry Tree Cancer Center
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
Study officials:
affiliation: University of New Maryland
name: Martin J. Edelman, MD
role: PRINCIPAL_INVESTIGATOR
References: