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

NCT00979212 | Completed Phase 2 Results DMC

• 4 other identifiers: RTOG-0839CDR0000654690NCT00979212NCI-2011-01970
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 31

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Survival

  Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study

• Patterns of First Failure

  Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.

• Percentage of Patients With Grade 3 or Higher Acute and Late Adverse Events

  Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.

• Surgical Morbidities in Patients With Resectable Disease at Reassessment

  From date of surgery to 30 days following surgery.

• 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.

Study Arms (2)

Induction CT+RT

ACTIVE COMPARATOR

Chemotherapy (paclitaxel and carboplatin) plus radiation therapy followed by surgery (if operable) followed by consolidation chemotherapy (paclitaxel and carboplatin)

Drug: carboplatin; Drug: paclitaxel; Procedure: surgery

Induction CT+RT+Panitumumab

EXPERIMENTAL

Panitumumab plus chemotherapy (paclitaxel and carboplatin) plus radiation therapy followed by surgery (if operable) followed by consolidation chemotherapy (paclitaxel and carboplatin)

Drug: panitumumab; Drug: carboplatin; Drug: paclitaxel; Procedure: surgery

Interventions

panitumumab DRUG

Induction: 2.5 mg/kg, IV, days 1, 8, 15, 22, 29, 36 of radiation therapy before administration of chemotherapy and radiation therapy.

Also known as: Vectibix

Induction CT+RT+Panitumumab

carboplatin DRUG

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.

Also known as: Paraplatin

Induction CT+RT; Induction CT+RT+Panitumumab

paclitaxel DRUG

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.

Also known as: Taxol, Abraxane

Induction CT+RT; Induction CT+RT+Panitumumab

surgery PROCEDURE

A lobectomy or pneumonectomy performed 4-6 weeks after completion of induction chemoradiation

Also known as: lobectomy, pneumonectomy

Induction CT+RT; Induction CT+RT+Panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (31)

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, 95608, United States

Location

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, 95815, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

CCOP - Ochsner

New Orleans, Louisiana, 70121, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

St. Agnes Hospital Cancer Center

Baltimore, Maryland, 21229, United States

Location

Cancer Institute at St. Joseph Medical Center

Towson, Maryland, 21204, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Methodist Estabrook Cancer Center

Omaha, Nebraska, 68114, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Adams Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Cherry Tree Cancer Center

Hanover, Pennsylvania, 17331, United States

Location

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, 19301-1792, United States

Location

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, 19107-5541, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, 19141, United States

Location

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

Reading, Pennsylvania, 19612-6052, United States

Location

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, 17405, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, 53295, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar

Interventions

Panitumumab; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Surgical Procedures, Operative; Anterior Temporal Lobectomy; Pneumonectomy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Neurosurgical Procedures; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Limitations and Caveats

Following a recommendation on July 13, 2015 by the NRG Data Monitoring Committee accrual was halted early after accruing only 71 of 97 patients due to unexpectedly high rates of grade 5 toxicity on the panitumumab arm.

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Martin J. Edelman, MD

  University of New Maryland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2009
• First Posted: September 17, 2009
• Study Start: February 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: May 20, 2022
• Last Updated: June 15, 2022
• Results First Posted: August 16, 2016

Record last verified: 2022-05

Locations

US (31)