Phase I/II NabPaclitaxel, Paclitaxel&Carboplatin w RTX Followed by Consolidation in Patients w Favorable Prognosis Inoperable Stage IIIA/B NSCLC

Study Overview
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Brief Summary
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The investigators propose this phase I/II study to use weekly Nab-Paclitaxel (Abraxane) and carboplatin with concurrent radiation in local-regionally advanced lung cancer. There are no published human studies combining Nab-Paclitaxel (Abraxane) with radiation. The investigators will first confirm the tolerated dose (TD) of concurrent Nab-Paclitaxel (Abraxane) at 50mg/m2, and then will begin enrolling patients into the phase II component using either Nab-Paclitaxel (Abraxane) at the TD with carboplatin concurrent with daily radiation or paclitaxel with carboplatin concurrent with daily radiation.

Official Title
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A RANDOMIZED PHASE I/II STUDY OF NAB-PACLITAXEL, OR PACLITAXEL, PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY FOLLoWED BY CONSOLIDATION IN PATIENTS WITH FAVORABLE PROGNOSIS INOPERABLE STAGE IIIA/B NON-SMALL CELL LUNG CANCER (NSCLC)

Conditions
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STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER

Intervention / Treatment
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* Drug: NAB-PACLITAXEL
* Drug: PACLITAXEL
* Drug: NAB-PACLITAXEL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented NSCLC; Patients must be M0. Patients with T1-T2 with N2 or T3N1-2 are eligible, if inoperable. Patients with T4 with any N or any T with N2 or N3 disease are eligible if unresectable. Patients with tumors adjacent to a vertebral body are eligible as long as all gross disease can be encompassed in the radiation boost field. The boost volume must be limited to < 50% of the ipsilateral lung volume. Patients with Zubrod performance status 0-1 Adequate hematologic function FEV1 with ≥ 1200 cc or ≥ 50% predicted Exclusion Criteria: Prior systemic chemotherapy (for lung cancer) and/or thoracic/neck radiotherapy for any reason and/or surgical resection of present cancer Exudative, bloody, or cytologically malignant effusions Prior therapy with any molecular targeted drugs (for lung cancer) Active pulmonary infection not responsive to conventional antibiotics Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease >2 (see Appendix B) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. Patients with > grade 1 neuropathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is Phase I/II study. Phase I has 1 arm and Phase II has 2 arms (total 3 arms)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PACLITAXEL (Phase II, Arm A)<br>PACLITAXEL PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY | Drug: PACLITAXEL<br> <br> |
| Experimental: NAB-PACLITAXEL (Phase II, Arm B)<br>NAB-PACLITAXEL PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY nab-Paclitaxel 40 mg/m2 IV/30min/wk x6 wks | Drug: NAB-PACLITAXEL<br>* nab-Paclitaxel 40 mg/m2 IV/30min/wk x6 wks<br>* Other names: Abraxan;|
| Experimental: NAB-PACLITAXEL (Phase I)<br>NAB-PACLITAXEL PLUS CARBOPLATIN WITH CONCURRENT RADIATION THERAPY nab-Paclitaxel 50 mg/m2 IV/30min/wk x6 wks | Drug: NAB-PACLITAXEL<br>* nab-Paclitaxel 50 mg/m2 IV/30min/wk x6 wks<br>* Other names: Abraxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Overall Survival (Phase II) | 2-year overall survival, as measured (by Kaplan-Meir method) as the percentage of patients who were randomized and received carboplatin/paclitaxel or carboplatin/nab-paclitaxel with radiation therapy survived for 2 years. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Feasibility of Concurrent Carboplatin/Nab-Paclitaxel and Radiation Therapy | The feasibility as measured by the number of participants who had grade 3 or higher radiation related esophagitis or pulmonary toxicity or chemotherapy related grade 4 hematological or other non-hematological toxicities occurring within 60 days of the start of treatment; compliance us defined as the completion of the treatment regimen with no more than minor variations. | 60 days of the start of treatment | 
| Overall Response Rate for the Patients Receiving Carboplatin/ Paclitaxel or Carboplatin/ Nab-paclitaxel With Radiation Therapy | The objective response rate (ORR) is defined as the percentage of participants achieving complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) criteria | 1,6,12,18,24 month | 
| Proportion of Participants With Progression-free Survival (Phase II) | Proportion of participants with progression free survival at 2 years is computed as the percentage of participants between randomization and local or regional progression, distant metastases, death, or last known follow-up. Estimates of progression free survival will be calculated using the Kaplan-Meir method. | 2 years | 
| Median Overall Survival (Phase II) | Median overall survival was based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive. | every 6 months up to 24 months (approx. 22 months) | 
| EuroQol-5Dimension (EQ-5D) MUS Score at Baseline | EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome.Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state. | Baseline | 
| EuroQol-5Dimension (EQ-5D) MUS Score at End of Treatment | EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome. Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state. | End of treatment (6 weeks) | 
| EuroQol-5Dimension (EQ-5D) VAS Score at Baseline | The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome. | Baseline | 
| EuroQol-5Dimension (EQ-5D) VAS Score at End of Treatment | The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome. | End of Treatment (6 weeks) | 
| EuroQol-5Dimension (EQ-5D) VAS Score at 24 Month Follow up | The second part of the EQ-5D is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point-interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Possible score ranges from 0-100 with higher scores indicating better outcome. | 24 month follow up | 
| EuroQol-5Dimension (EQ-5D) MUS Score at 24 Month | EQ-5D is a two-part questionnaire. The first part of mean utility score (MUS) consists of five items addressing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on three levels: 1-no problems, 2- slight problems, and 3-moderate problems, 4-severe problems, 5-extreme problems. Possible score ranges from 5-25 with higher scores indicating worse outcome.Both the five-item index score and the VAS score are transformed into a utility score between 0-worst health state and 1-best health state. | 24 month follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER