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

NCT ID: NCT00979212

Last Updated: 2022-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2022-05-20

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction CT+RT

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

Group Type: ACTIVE_COMPARATOR

carboplatin

Intervention Type: 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.

paclitaxel

Intervention Type: 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.

surgery

Intervention Type: PROCEDURE

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

Induction CT+RT+Panitumumab

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

Group Type: EXPERIMENTAL

panitumumab

Intervention Type: DRUG

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

carboplatin

Intervention Type: 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.

paclitaxel

Intervention Type: 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.

surgery

Intervention Type: PROCEDURE

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

Interventions

panitumumab

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

surgery

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

Intervention Type: PROCEDURE

Other Intervention Names

Vectibix; Paraplatin; Taxol; Abraxane; lobectomy; pneumonectomy

Eligibility Criteria

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin J. Edelman, MD

Role: PRINCIPAL_INVESTIGATOR

University of New Maryland

Locations

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, United States

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, United States

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, United States

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Cancer Institute at St. Joseph Medical Center

Towson, Maryland, United States

Boston University Cancer Research Center

Boston, Massachusetts, United States

Fairview Southdale Hospital

Edina, Minnesota, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

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

Rochester, New York, United States

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, United States

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Adams Cancer Center

Gettysburg, Pennsylvania, United States

Cherry Tree Cancer Center

Hanover, Pennsylvania, United States

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

Reading, Pennsylvania, United States

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

CDR0000654690

Identifier Type: -

Identifier Source: secondary_id

NCT00979212

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-01970

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG-0839

Identifier Type: -

Identifier Source: org_study_id