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

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)

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 Overview

• Status: Completed
• Conditions: STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER
• Intervention / Treatment: Drug: PACLITAXEL; Drug: NAB-PACLITAXEL; Drug: NAB-PACLITAXEL

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75239
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Celgene
• Investigators: Principal Investigator: Yuanyuan Zhang, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2013
• Primary Completion (Actual): June 3, 2019
• Study Completion (Actual): June 3, 2019

Study Registration Dates

• First Submitted: December 20, 2012
• First Submitted That Met QC Criteria: December 27, 2012
• First Posted (Estimate): December 28, 2012

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: STAGE IIIA/B NSCLC / INOPERABLE LUNG CANCER
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: STU 062012-053