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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: paclitaxel; Radiation: radiation therapy; Radiation: stereotactic body radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center - Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• Prior history of lung cancer
• Pregnancy
• Prior history of radiation to the chest

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (radiation therapy, carboplatin, paclitaxel, 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.	Drug: carboplatin; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Drug: paclitaxel; Other Names: Taxol; Anzatax; Asotax; TAX; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation; Radiation: stereotactic body radiation therapy; Undergo SBRT; Other Names: SBRT; stereotactic radiation therapy; stereotactic radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Acute toxicities associated with this regimen using CTCAE v.4	Crude rates of grade 3 and greater acute toxicities will be reported.	Up to 90 days
Late toxicities associated with this regimen using CTCAE v.4	Crude rates of grade 3 and greater late toxicities will be reported.	After 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control	Will be calculated for the entire cohort using Kaplan-Meier methodology.	Up to 5 years
Distant metastasis	Will be calculated for the entire cohort using Kaplan-Meier methodology.	Up to 5 years
Patterns of failure	Will be assessed with standard follow-up imaging, and the percentages of in-field failures versus regional nodal failures calculated.	Up to 5 years
Overall survival	Will be calculated for the entire cohort using Kaplan-Meier methodology.	At 1 year
Overall survival	Will be calculated for the entire cohort using Kaplan-Meier methodology.	At 2 years
Overall survival	Will be calculated for the entire cohort using Kaplan-Meier methodology.	At 5 years

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Washington University Siteman Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 4, 2012
• Primary Completion (ANTICIPATED): May 31, 2022
• Study Completion (ANTICIPATED): May 31, 2022

Study Registration Dates

• First Submitted: October 18, 2012
• First Submitted That Met QC Criteria: October 18, 2012
• First Posted (ESTIMATE): October 22, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: IRB00056552; NCI-2012-01934 (REGISTRY: CTRP (Clinical Trial Reporting Program)); RAD2179-12 (OTHER: Winship Cancer Institute)