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

Study Overview
=================
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.

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

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
-----------------
* Drug: Paclitaxel poliglumex
* Drug: Carboplatin
* Radiation: External beam radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1 (first 12 eligible patients)<br>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. | Drug: Paclitaxel poliglumex<br> <br> * Other names: Xyotax;Drug: Carboplatin<br> <br> * Other names: Paraplatin;Radiation: External beam radiation therapy<br> <br> |
| Experimental: Cohort 2 (remaining patients)<br>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. | Drug: Paclitaxel poliglumex<br> <br> * Other names: Xyotax;Drug: Carboplatin<br> <br> * Other names: Paraplatin;Radiation: External beam radiation therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Rate | OS = time from patient registration to death of all causes Estimated using Kaplan Meier | 6 months | 
| Overall Survival (OS) | OS = time from patient registration to death of all causes | Completion of follow-up (follow-up ranged from 3 months to 6 years) | 

Secondary Outcome Measures

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