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

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT01486602

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

70.5

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin Drug: paclitaxel Radiation: radiation therapy	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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 Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Jan 1, 2017

Actual Study Completion Date :

Jan 16, 2018

Arms and Interventions

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

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

Drug: paclitaxel

Radiation: radiation therapy

Defined per the protocol

Outcome Measures

Primary Outcome Measures

Maximum-tolerated RT dose fraction [Up to 28 months]

Secondary Outcome Measures

Radiographic response [Up to 5 years]
Metabolic response [Up to 5 years]
Rates of progression: local/regional/distant [Up to 5 years]
Progression-free survival [Up to 5 years]
Overall survival [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Histologically or cytologically documented non-small cell lung cancer
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
Thoracic disease without supraclavicular or contralateral hilar involvement
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
No prior radiotherapy or chemotherapy for NSCLC
No prior mediastinal or thoracic radiotherapy
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
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

Eastern Cooperative Oncology Group (ECOG) performance status 0-1
No patients that are known to be pregnant or nursing
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
3	Moores University of California San Diego Cancer Center	La Jolla	California	United States	92093-0987
4	University of Chicago	Chicago	Illinois	United States	60637
5	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
8	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7305
9	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157-1030
10	Rhode Island Hospital	Providence	Rhode Island	United States	02903
11	University of Vermont	Burlington	Vermont	United States	05401