Specialized Radiation Therapy and Chemotherapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Phase I Study of Accelerated Hypofractionated Radiation Therapy With Concomitant Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer

This phase I trial studies the side effects and the best dose of hypofractionated radiation therapy when given together with chemotherapy in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hypofractionated radiation therapy together with chemotherapy may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: paclitaxel; Radiation: radiation therapy

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerable radiotherapy (RT) dose fraction for accelerated hypofractionated radiotherapy with concurrent chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the rate of radiographic response to treatment. II. To estimate the rates of progression: local/regional/distant. III. To estimate the progression-free survival. IV. To estimate the overall survival.

OUTLINE: This is a dose-escalation study of accelerated hypofractionated radiotherapy.

CONCURRENT THERAPY: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30-60 minutes on days 1 and 8. Treatment repeats every 14 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo accelerated hypofractionated radiotherapy using 3-dimensional conformal radiation therapy or intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for approximately 4-5.5 weeks.

CONSOLIDATION THERAPY: Beginning 4 weeks after completion of radiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month, every 3 months for 2 years, and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • California
    • La Jolla, California, United States, 92093-0987
      • Moores University of California San Diego Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New York
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7305
      • University of North Carolina - Chapel Hill
    • Winston-Salem, North Carolina, United States, 27157-1030
      • Wake Forest University Health Sciences
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

1. Histologically or cytologically documented non-small cell lung cancer
2. Stage IIIA or IIIB non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) version 7; patients who present with N2 or N3 disease and an undetectable primary tumor are also eligible
3. Thoracic disease without supraclavicular or contralateral hilar involvement
4. When pleural fluid is visible on both computed tomography (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; patients with effusions that are minimal (i.e., not visible on chest x-ray) and too small to safely tap are eligible
5. No prior radiotherapy or chemotherapy for NSCLC
6. No prior mediastinal or thoracic radiotherapy
7. Patients with complete surgical resection of disease are not eligible, however; patients with surgical resection and measurable gross residual disease present on imaging are considered eligible

8. Patients must have measurable disease

   • Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral CT scan

   • Patients with non-measurable disease are not eligible; all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions; lesions that are considered non-measurable include the following:

     • Bone lesions
     • Leptomeningeal disease
     • Ascites
     • Pleural/pericardial effusion
     • Inflammatory breast disease
     • Lymphangitis cutis/pulmonis
     • Abdominal masses that are not confirmed and followed by imaging techniques
     • Cystic lesions
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
10. No patients that are known to be pregnant or nursing
11. Granulocytes ≥ 1,500/μl Platelet count ≥ 100,000/μl Bilirubin ≤ 1.5 times upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxalo-acetic transaminase [SGOT]) ≤ 2.0 times ULN Serum creatinine ≤ 1.5 times ULN OR calculated creatinine clearance >= 70 mL/min FEV-1 ≥ 1.2 L/sec or 50% predicted

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Concurrent therapy + consolidation therapy; Concurrent Therapy (1 cycle = 14 days, Cycles 1-3): Patients will receive paclitaxel 45 mg/m^2 by IV over 1 hour weekly followed by carboplatin AUC 2 by IV over 30-60 minutes for 4 weeks (there will be no chemotherapy during Cycle 3). Patients will receive radiotherapy concurrently for up to 5.5 weeks, depending on the cohorts the patient is registered defined per the protocol. Consolidation Therapy (1 cycle = 21 days, Cycles 4-5): Four weeks following the end of radiotherapy patients will receive paclitaxel 200 mg/m^2 by IV over 3 hours followed by carboplatin AUC 6 by IV over 30-60 minutes on day 1 of each 21 day cycle for a total of 2 cycles (days 1 and 22).

Drug: carboplatin; IV; Drug: paclitaxel; IV; Radiation: radiation therapy; Defined per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum-tolerated RT dose fraction	Up to 28 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Up to 5 years
Overall survival	Up to 5 years
Radiographic response	Up to 5 years
Metabolic response	Up to 5 years
Rates of progression: local/regional/distant	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: James J. Urbanic, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 16, 2018

Study Registration Dates

• First Submitted: December 2, 2011
• First Submitted That Met QC Criteria: December 2, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: January 17, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer
• 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: CALGB 31102; U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000719011 (Registry Identifier: Physician Data Query); NCI-2012-00087 (Registry Identifier: NCI Clinical Trial Reporting Program)