A Phase II Study of Radiation Therapy, Paclitaxel Poliglumex, and Carboplatin in Stage III Non-Small Cell Lung Cancer

Phase 2

Terminated

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: Paclitaxel poliglumex
Drug: Carboplatin
Radiation: External beam radiation therapy

Registration Number: NCT00352690

Lead Sponsor: Washington University School of Medicine

Brief Summary: This study is intended to evaluate the role of paclitaxel poliglumex and carboplatin in the treatment of unresectable Stage III non-small cell lung cancer along with radiation therapy in a multi-institutional trial. Consolidation chemotherapy with paclitaxel poliglumex and carboplatin will follow the completion of chemoradiation.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Histologically or cytologically documented NSCLC, including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas).
Eligible Disease Stages: Inoperable IIIA and Selected IIIB
Local radiation oncologist must approve patient eligibility prior to entry on study.
Patients must have measurable disease.
Prior Therapy:
- ≥ 2 weeks since formal exploratory thoracotomy.
- No prior chemotherapy or radiation therapy for NSCLC.
ECOG performance status 0-1
Required Initial Laboratory Values (must be submitted within 16 days prior to registration):
- Granulocytes ≥ 1,500/µl
- Platelets ≥ 100,000/µl
- Calculated Creatinine Clearance ≥ 20 cc/min
- Bilirubin < 1.5 mg/dl
- AST (SGOT) < 2 x ULN
- INR > 0.8 < 1.2* *Values apply exclusively to patients not being treated with warfarin. Values for patients being treating with warfarin should fall within the following therapeutic range: > 2.0 < 3.0.

Exclusion Criteria

Currently active second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
Pregnant or nursing because of significant risk to the fetus/infant.
Age <18 years.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
No HIV-positive patients receiving combination anti-retroviral therapy. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy
One-second forced expiratory volume (FEV1) <50% or hemoglobin-corrected carbon monoxide diffusion capacity (DLCO) <50% of predicted, as measured within 21 days of study entry
Symptoms of esophageal dysfunction (dysphagia, odynophagia, or inability to swallow solid food) within 4 weeks prior to study randomization. Patients must not require prophylactic placement of percutaneous enterogastrostomy (PEG) tube or other non-oral nutritional supplement methods
Weight loss of > 10% in the past 3 months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 (first 12 eligible patients)	External beam radiation therapy	Paclitaxel poliglumex 135 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles. Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles. Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions. Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Cohort 2 (remaining patients)	External beam radiation therapy	Paclitaxel poliglumex 175 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles. Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles. Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions. Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Cohort 2 (remaining patients)	Carboplatin	Paclitaxel poliglumex 175 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles. Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles. Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions. Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Cohort 1 (first 12 eligible patients)	Carboplatin	Paclitaxel poliglumex 135 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles. Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles. Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions. Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Cohort 1 (first 12 eligible patients)	Paclitaxel poliglumex	Paclitaxel poliglumex 135 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles. Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles. Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions. Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.
Cohort 2 (remaining patients)	Paclitaxel poliglumex	Paclitaxel poliglumex 175 mg/m2 IV on day 1 of each 21 day cycle for a total of 2 cycles. Carboplatin AUC=5 IV over 30 minutes on day 1 of each 21 day cycle for a total of 2 cycles. Thoracic radiation therapy starting day 1 consisting of 66 Gy delivered in 2 Gy daily fractions. Paclitaxel poliglumex 175 mg/m2 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles. Carboplatin AUC=6 IV beginning 3-5 weeks after completion of radiation therapy on day 1 every 21 days for a total of 2 cycles.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Completion of follow-up (follow-up ranged from 3 months to 6 years)	OS = time from patient registration to death of all causes
Overall Survival (OS) Rate	6 months	* OS = time from patient registration to death of all causes * Estimated using Kaplan Meier

Secondary Outcome Measures

Name	Time	Method
Response Rates	4 years	Overall best response using RECIST 1.0
Incidence and Severity of Radiation-induced Esophagitis	30 days following completion of treatment (approximately 114 days)
Failure-free Survival (FFS)	Completion of follow-up (follow-up ranged from 3 months to 6 years)	The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first)
Failure-free Survival (FFS) Rate	6 months	* The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first) * Estimated using Kaplan Meier
Incidence and Severity of Radiation-induced Pneumonitis	30 days following completion of treatment (approximately 114 days)

Trial Locations

Locations (8): University of Kansas
🇺🇸
Lawrence, Kansas, United States
Rush University Medical College
🇺🇸
Chicago, Illinois, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
University of Missouri, Columbia
🇺🇸
Columbia, Missouri, United States
Washington University School of Medicine
🇺🇸
St. Louis, Missouri, United States
SUNY Upstate Medical University
🇺🇸
Syracuse, New York, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
University of Minnesota, Twin Cities
🇺🇸
Minneapolis, Minnesota, United States