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

University of Texas Southwestern Medical Center98 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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

Locations (5)

University of Rochester

Rochester, New York, United States

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: 2 years

Secondary Outcomes

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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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."

Time frame: 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."

Time frame: 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.