Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Previously Treated Advanced Non-small Cell Lung Cancer

A Phase II Study of Weekly Abraxane for Patients With Advanced NSCLC With EGFR Mutations or With Durable Response to an EGFR Tyrosine Kinase Inhibitor Following Front Line Therapy With EGFR Tyrosine Kinase Inhibitors

This research study examines the use of Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) in patients with lung cancer. Abraxane is a chemotherapy approved to treat patients with breast cancer. Doctors want to know if Abraxane is safe and effective in treating patients with lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) and epidermal growth factor receptor (EGFR) mutations.

Study Overview

• Status: Completed
• Conditions: Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the overall response rate of weekly nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations following front-line therapy with EGFR tyrosine kinase inhibitors (TKI).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of weekly nab-paclitaxel in patients with advanced NSCLC with EGFR mutations following front-line therapy with an EGFR TKI.

II. To evaluate the time-to-progression and overall survival.

OUTLINE:

Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 3 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Montana
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Port Angeles, Washington, United States, 98362
      • Olympic Medical Center
    • Redmond, Washington, United States, 98052
      • Group Health Cooperative
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium
    • Spokane, Washington, United States, 99216
      • Spokane Valley Cancer Center-Mission
    • Tacoma, Washington, United States, 98415
      • MultiCare Health System
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically confirmed non-small cell lung cancer with documented EGFR mutation in tumor deoxyribonucleic acid (DNA) or complete/partial response to first line EGFR tyrosine kinase inhibitors with > or = to 6 months duration of response in patients who do not have a confirmed EGFR mutation
• At least one site of measurable disease as determined by the Investigator, using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Progressive disease with radiographic evidence of disease progression per investigator assessment during therapy with an EGFR tyrosine kinase inhibitor in the metastatic setting; patients may continue EGFR inhibitor therapy throughout the screening period until the day prior to nab-paclitaxel treatment initiation
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 at the time of informed consent
• Platelet count >= 100,000/uL
• Absolute neutrophil count >= 1,500/uL
• Hemoglobin >= 9 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = < 2.5 times upper limit of normal
• Alkaline phosphatase =< 2.5 times upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
• Bilirubin =< 1.5 mg/dL
• Creatinine =< 1.5 mg/dL
• Women of child-bearing potential (WOCP) and sexually active men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, during treatment and for three months after completing treatment
• Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential
• Life expectancy of > 12 weeks
• Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

• Prior conventional cytotoxic chemotherapy for metastatic or recurrent disease; prior adjuvant, neoadjuvant or chemoradiotherapy for NSCLC is permitted, provided at least 6 months elapsed prior to documented metastatic recurrence
• A single dose of a platinum doublet discontinued due to intolerability without evidence of disease progression is permitted
• Patient is < 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention
• Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment with surgery, radiation or both; in addition, they must be off corticosteroids
• Radiotherapy within 7 days of study treatment
• Peripheral neuropathy grade 2 or greater
• Grade III/IV congestive heart failure, as defined by New York Heart Association (NYHA) criteria, or myocardial infarction within 6 months
• Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
• Patient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosis
• Major surgery within 21 days of study treatment; minor surgery within 2 weeks of study treatment; placement of vascular access device and biopsies allowed and is not considered major or minor surgery
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
• Pregnant or breast feeding females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (paclitaxel albumin-stabilized nanoparticle formula); Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Given IV; Other Names: ABI-007; Abraxane; Albumin-bound Paclitaxel; ABI 007; Albumin-Stabilized Nanoparticle Paclitaxel; Nanoparticle Albumin-bound Paclitaxel; Nanoparticle Paclitaxel; nab-paclitaxel; protein-bound paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (Complete and Partial Response) Defined by RECIST 1.1 Criteria	The response rate as the proportion and 95% confidence interval of patients who achieved a complete response or partial response will be calculated.	Assessed every two cycles from date of first study therapy until documented disease progression, date of death, unacceptable toxicity, or withdrawal of patient consent, whichever occurs first, assessed up to 60 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Percentage of Patients Experiencing Toxicity Within a Clinically Significant Category Defined as Neutropenia, Neutropenic Fever, or Neuropathy.	Toxicity rates will be described as percentage of patient who experienced a Grade 3 or higher clinically significant toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.	Collected from the time patient received the first dose of study therapy through 30 days following the last dose of study therapy or the start of a new cancer therapy, whichever occurred first, assessed up to 64 weeks.
Overall Survival	Will report as median values with their respective 95% confidence intervals will be reported. Time to event distribution will be estimated using Kaplan-Meier method.	Assessed from date of patient consent until date of death from any cause or withdrawal of patient consent, whichever occurs first, assessed up to 305 weeks.
Overall Percentage of Patients Experiencing Grade 3 or Higher Toxicity.	Toxicity rates will be described as percentage of patients experiencing Grade 3 or higher toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.	Collected from the time patient received the first dose of study therapy through 30 days following the last dose of study therapy or the start of a new cancer therapy, whichever occurred first, assessed up to 64 weeks.
Time to Progression.	Reported as median values with their respective 95% confidence intervals for patients who were assessed. Time to event distribution will be estimated using the Kaplan-Meier method.	Assessed from date of patient consent until documented disease progression, date of death from any cause, start of new anti-cancer therapy, or withdrawal of patient consent, whichever occurs first, assessed up to 60 weeks.

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI); Celgene Corporation
• Investigators: Principal Investigator: Christina Baik, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2012
• Primary Completion (Actual): October 24, 2017
• Study Completion: April 29, 2019

Study Registration Dates

• First Submitted: June 13, 2012
• First Submitted That Met QC Criteria: June 13, 2012
• First Posted (Estimate): June 15, 2012

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: June 26, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: 7755 (Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2012-00865 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RG1712044 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)