Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00979212
• Other study ID #: RTOG-0839
• Secondary ID: CDR0000654690NCI
• Status: Completed
• Phase: Phase 2
• Start date: February 2011
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: May 20, 2022
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• panitumumab
Induction: 2.5 mg/kg, IV, days 1, 8, 15, 22, 29, 36 of radiation therapy before administration of chemotherapy and radiation therapy.
• carboplatin
Induction: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. Consolidation, 6-12 weeks following surgery, AUC=6, IV, days 1 and 22.
• paclitaxel
Induction: 50 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. Consolidation, 6-12 weeks following surgery, 200 mg/m2, IV, days 1 and 22.

Procedure:
• surgery
A lobectomy or pneumonectomy performed 4-6 weeks after completion of induction chemoradiation

Locations

Country	Name	City	State
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Cancer Institute at St. Joseph Medical Center	Towson	Maryland
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mediastinal Nodal Clearance After Completion of Induction Chemoradiotherapy With or Without Panitumumab.	The assessment of whether mediastinal nodes which were involved at the time of study registration were clear of disease following induction chemoradiotherapy with or without panitumumab; the assessment is made at the time of surgery 4-6 weeks after chemoradiation. If surgery could not be performed, the patient was considered as not having had mediastinal nodal clearance.	From date of randomization to time of protocol surgery, approximately 12 weeks.
Secondary	Overall Survival	Survival time was calculated from the date of randomization to the date of death from any cause or the date of last follow-up. The Kaplan-Meier method was used to estimate the overall survival rates. One-year survival rates were estimated, not compared.	Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study
Secondary	Patterns of First Failure	The first failure site will be tabulated, not compared.	Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
Secondary	Percentage of Patients With Grade 3 or Higher Acute and Late Adverse Events	Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Does not include surgical morbidities. An acute adverse event is defined as any grade 3 or worse toxicity occurring during protocol treatment and within 30 days from the end of protocol treatment that is possibly, probably, or definitely related to treatment. Acute adverse events are any adverse events occurring within 30 days of the end of all protocol treatment. Late adverse events are any adverse events occurring after 30 days after the end of all protocol treatment.	Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
Secondary	Surgical Morbidities in Patients With Resectable Disease at Reassessment	A surgical morbidity is any toxicity occurring within 30 days of protocol surgery, as evaluated using CTCAE v4.0. Rates of grade 3 and higher surgical morbidity were calculated; the rates across arms were not compared.	From date of surgery to 30 days following surgery.
Secondary	Ability of FDG-PET/CT Scan Data to Predict Outcome		Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.
Secondary	Response Rate	Patients are assessed for best response to protocol treatment using the RECIST criteria. The response rate was calculated as the number of patients who have a complete response (CR) or partial response (PR) divided by the total number of analyzable patients at completion of induction chemoradiation +/- panitumumab and prior to anticipated surgery in each arm. Patients without a documented assessment are considered as not having a CR or PR. Rates are not compared across arms.	From date of randomization to time of protocol surgery, approximately 12 weeks.