An Alternative Radiation Fractionation Strategy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase 1

Conditions: Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer

Interventions: Radiation: stereotactic body radiation therapy
Drug: carboplatin
Drug: paclitaxel
Radiation: radiation therapy

Brief Summary: This phase I trial studies the best dose of radiation therapy in treating patients with locally advanced non-small cell lung cancer that cannot be removed by surgery. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy, such as stereotactic body radiation therapy (SBRT), that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. SBRT has been shown to provide excellent results when used in early stage lung cancer, but has not yet been applied to patients with more advanced disease.

Detailed Description: PRIMARY OBJECTIVE:

To test the safety and tolerability of an alternative fractionation regimen in locally advanced non-small cell lung cancer (NSCLC), consisting of 44 Gy with concurrent chemotherapy followed by a stereotactic body radiation therapy (SBRT) boost to remaining parenchymal and nodal disease. The maximum tolerated dose of the SBRT boost will be determined.

SECONDARY OBJECTIVES:

1. To assess local control.

2. To assess distant metastasis and patterns of failure.

3. To assess overall survival at 1 and 2 years.

OUTLINE: This is a dose-escalation study of radiation therapy and SBRT.

Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.

After completion of study treatment, patients are followed up for 5 years.

Recruitment & Eligibility

Inclusion Criteria

Biopsy proven NSCLC, within 8 weeks prior to patient registration
Unresectable disease
Clinical stage Tx, T1-T4, N1-3, M0
Karnofsky performance status (KPS) ≥ 70
Pretreatment positron emission tomography (PET) CT scan to rule out metastatic disease
- The primary tumor may not be larger than 8 cm in maximum dimension
- If the primary tumor is central in location, defined as within 2 cm from the tracheobronchial tree, it must be no larger than 5 cm
- Mediastinal and hilar lymphadenopathy can be no larger than 5 cm at any nodal station
Pretreatment brain CT with contrast or brain MRI to rule out metastases
Pathologic assessment of the mediastinum to document involved nodal stations
All of the above inclusion criteria must occur within 8 weeks prior to patient registration, with the exception of pathologic assessment of the mediastinum and biopsy to confirm NSCLC, which can be done within 12 weeks of patient registration

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)	radiation therapy	Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.
Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)	stereotactic body radiation therapy	Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.
Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)	carboplatin	Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.
Treatment (radiation therapy, carboplatin, paclitaxel, SBRT)	paclitaxel	Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart.

Primary Outcome Measures

Name	Time	Method
Acute toxicities associated with this regimen using CTCAE v.4	Up to 90 days	Crude rates of grade 3 and greater acute toxicities will be reported.
Late toxicities associated with this regimen using CTCAE v.4	After 90 days	Crude rates of grade 3 and greater late toxicities will be reported.
Maximum tolerated dose (MTD) defined to be the dose level that results in a probability equal to 0.33 that a dose limiting toxicity (DLT) will be manifest using Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v.4)	Up to 1 year

Secondary Outcome Measures

Name	Time	Method
Patterns of failure	Up to 5 years	Will be assessed with standard follow-up imaging, and the percentages of in-field failures versus regional nodal failures calculated.
Distant metastasis	Up to 5 years	Will be calculated for the entire cohort using Kaplan-Meier methodology.
Overall survival	At 5 years	Will be calculated for the entire cohort using Kaplan-Meier methodology.
Local control	Up to 5 years	Will be calculated for the entire cohort using Kaplan-Meier methodology.

Locations (4): Siteman Cancer Center - Washington University
🇺🇸
Saint Louis, Missouri, United States
Emory University Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Emory University Hospital Midtown
🇺🇸
Atlanta, Georgia, United States
Grady Health System
🇺🇸
Atlanta, Georgia, United States