Albumin-bound Paclitaxel (ABI-007) for Patients With Advanced Non-Small Cell Lung Cancer

October 16, 2019 updated by: Celgene

A Randomized, Phase III Trial of ABI-007 and Carboplatin Compared With Taxol and Carboplatin as First-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

The purpose of this study is to compare disease response of Albumin-bound paclitaxel (ABI-007) plus Carboplatin versus Taxol and Carboplatin as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1052

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • New Westminster, British Columbia, Canada, V3L 3W4
        • Royal Columbian Hospital
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • William Osler Health Centre, Brampton Clinic
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
      • Toronto, Ontario, Canada, M4C3E7
        • Toronto East General Hospital
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • Hopital Du Sacre-Coeur de Montreal
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill University- Dept. of Oncology
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35805
        • Clearview Cancer Institute Oncology Specialties, P.C.
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
        • Genesis Cancer Center- Hot Springs
      • Little Rock, Arkansas, United States, 72205
        • Little Rock Hematology Oncology Associates
    • California
      • Anaheim, California, United States, 92801
        • Pacific Cancer Medical Center, Inc.
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center
      • Escondido, California, United States, 92064
        • Southwest Cancer Care
      • Fountain Valley, California, United States, 92708
        • Robert A. Moss, MD, FACP, Inc.
      • Long Beach, California, United States, 90813
        • Pacific Shores Medical Group
      • Oxnard, California, United States, 93030
        • Ventura County Hematology-Oncology Specialists
      • Palms Springs, California, United States, 92262
        • Comprehensice Cancer Ctr.
    • Florida
      • Saint Petersburg, Florida, United States, 33705
        • Gulf Coast Oncology Associates
      • Tavares, Florida, United States, 32778
        • Lake County Oncology and Hematology, PA
    • Georgia
      • Albany, Georgia, United States, 31701
        • Phoebe Cancer Center
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kentuckiana Cancer Institute, PLLC
    • Maine
      • Portland, Maine, United States, 04101
        • Mercy Hospital
      • Scarborough, Maine, United States, 04074
        • Maine Center For Cancer Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Mercy Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • St. Louis University
    • New Jersey
      • Belleville, New Jersey, United States, 07109
        • Essex Oncology of North Jersey
    • New York
      • Cooperstown, New York, United States, 13326
        • Mary Imogene Bassett Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
    • Pennsylvania
      • Langhorne, Pennsylvania, United States, 19047
        • St. Mary Medical Center- Oncology, Hematology PC
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Duncanville, Texas, United States, 75137
        • Dallas Oncology Consultants, PA
      • Fort Worth, Texas, United States, 76104
        • The Center for Cancers and Blood Disorders
      • Lubbock, Texas, United States, 79410
        • Joe Arrington Cancer Research and Treatment Center
      • Tyler, Texas, United States, 75701
        • Tyler Hematology Oncology
      • Tyler, Texas, United States, 75701
        • Blood and Cancer Center of East Texas
    • Vermont
      • Burlington, Vermont, United States, 05405
        • Fletcher Allen Health Care
    • Virginia
      • Abingdon, Virginia, United States, 24211
        • Cancer Outreach Associates, Pc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Histologically or cytologically confirmed stage IIIB or IV non-small cell lung cancer (NSCLC)

  • Male or non-pregnant and non-lactating female, and equal or greater than age 18

    • If a female patient is of child-bearing potential, as evidence by regular menstrual periods, she must have a negative serum pregnancy test (beta human chorionic gonadotropin [βhCG]) documented within 72 hours of the first administration of study drug
    • If sexually active, the patient must agree to utilize contraception considered adequate and appropriate by the investigator
  • No other current active malignancy
  • Radiographically-documented measurable disease (defined by the presence of at least 1 radiographically documented measurable lesion)
  • Patients must have received no prior chemotherapy for the treatment of metastatic disease. Adjuvant chemotherapy permitted providing cytotoxic chemotherapy was completed 12 months prior to starting the study

  • Patient has the following blood counts at baseline:

    • Absolute neutrophil count (ANC) greater than or equal to 1.5x10^9/L
    • Platelets greater than or equal to 100x10^9/L
    • Hemoglobin (Hgb) greater than or equal to 9 g/dL

  • Patient has the following blood chemistry levels at baseline:

    • Aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT) less than or equal to 2.5 x upper limit of normal range (ULN) or less than or equal to 5.0 x ULN if liver metastases;
    • Total bilirubin less than or equal to ULN
    • Creatinine less than or equal to 1.5 mg/dL
  • Expected survival of greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Patient or his/her legally authorized representative or guardian has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities

Exclusion Criteria:

  • Evidence of active brain metastases, including leptomeningeal involvement. Prior evidence of brain metastasis permitted only if treated and stable and off therapy for greater than or equal to 1 month
  • The only evidence of disease is non-measurable
  • Patient has pre-existing peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events [CTCAE] Version 3).
  • Patient received radiotherapy in the last 4 weeks, except if to a non-target lesion only. Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed
  • Patient has a clinically significant concurrent illness
  • Patient has received treatment with any investigational drug within the previous 4 weeks
  • Patient has a history of allergy or hypersensitivity to any of the study drugs
  • Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug
  • Patient is enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Albumin-bound paclitaxel + Carboplatin
Participants received albumin-bound paclitaxel (ABRAXANE®) 100 mg/m^2 administered as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of each 21-day cycle. Carboplatin was given at an Area Under the Curve (AUC) = 6 mg*min/mL on Day 1 only of each 21-day cycle, beginning immediately after the completion of albumin-bound paclitaxel administration. Participants could continue treatment at the investigator's discretion until disease progression, development of an unacceptable toxicity, or withdrawal of consent.
Drug: Albumin-bound paclitaxel
Administered by intravenous infusion.
Other Names:
  • ABI-007
  • ABRAXANE®
  • nab®-paclitaxel
Drug: Carboplatin
Administered by intravenous infusion. Dosing was based on the Calvert formula: carboplatin dose (mg) = (Target AUC) x (glomerular filtration rate [GFR] + 25). For the purposes of this protocol, the GFR is considered to be equivalent to creatinine clearance (calculated by the method of Cockcroft and Gault, 1976).
Active Comparator: Paclitaxel + Carboplatin
Participants received 200 mg/m^2 paclitaxel (Taxol®) administered by intravenous infusion followed by carboplatin at AUC = 6 mg*min/mL on Day 1 of a 21 day cycle. Participants could continue treatment at the investigator's discretion until disease progression, development of an unacceptable toxicity, or withdrawal of consent.
Drug: Carboplatin
Administered by intravenous infusion. Dosing was based on the Calvert formula: carboplatin dose (mg) = (Target AUC) x (glomerular filtration rate [GFR] + 25). For the purposes of this protocol, the GFR is considered to be equivalent to creatinine clearance (calculated by the method of Cockcroft and Gault, 1976).
Drug: Paclitaxel
Administered by intravenous infusion.
Other Names:
  • Taxol®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment
Time Frame: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.

Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0.

A complete response was defined as a disappearance of all target and non-target lesions and no new lesions.

Partial response was defined as ≥ 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, and the persistence of one or more non-target lesions not qualifying for CR or Progressive Disease (the "unequivocal progression" of existing non-target lesion(s) or appearance of one or more new lesions).
Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival by Blinded Radiology Assessment
Time Frame: Assessed every 6 weeks until progression or death, up to 38 months

Progression free survival time was defined as the time from the day of randomization to the start of disease progression or death (any cause), whichever occurred first, based on the blinded radiological review response assessment. Progressive disease was defined as a ≥ 20% increase in the SLD of target lesions, taking as reference the nadir SLD recorded since the treatment started, or the presence of one or more new lesions, or the "unequivocal progression" of existing non-target lesion(s) or appearance of one or more new lesion(s).

Participants who did not have disease progression or had not died were censored at the last visit they were documented as progression free. If palliative radiotherapy or surgery at lesion sites occurred, the participant was censored at the last date without documented progression prior to radiotherapy or surgery. In follow-up, participants who began new therapy prior to progression were censored at the last documented date as progression-free.
Assessed every 6 weeks until progression or death, up to 38 months
Overall Participant Survival
Time Frame: Up to 38 months
Overall survival was defined as the time from the day of randomization to participant death (due to any cause), as assessed by post study follow-up performed monthly for 6 months and every 3 months thereafter for 12 months. All participants who were lost to the follow-up prior to the end of the trial or who completed the 18 month follow up phase were censored at last known time the participant was alive.
Up to 38 months
Percentage of Participants With Controlled Disease
Time Frame: Assessed every 6 weeks, up to 22 months
Controlled disease was defined as the percentage of participants with stable disease for ≥ 16 weeks or confirmed complete or partial overall response, based on blinded radiological assessment. Stable disease was defined as neither sufficient shrinkage of target lesions to qualify for Partial Response, nor sufficient increase to qualify for Progressive Disease, or the persistence of one or more non-target lesions not qualifying for Complete Response or Progressive Disease.
Assessed every 6 weeks, up to 22 months
Duration of Response in Responding Patients
Time Frame: Assessed every 6 weeks, up to 38 months
Duration of response was assessed by progression free survival for participants who achieved a confirmed complete response or partial response based on blinded radiological assessment.
Assessed every 6 weeks, up to 38 months
Number of Participants With Adverse Events (AEs)
Time Frame: Up to 38 months
A Treatment-emergent AE was any AE that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug or end of study whichever is later. Treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence at any dose that: is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
Up to 38 months
Pharmacokinetic (PK) Parameters
Time Frame: Blood samples for PK analyses were taken during Cycle 1 at 0.25, 3.5 and 24 hours post-infusion.
Blood samples for PK analyses were taken during Cycle 1 at 0.25, 3.5 and 24 hours post-infusion.
SPARC Status and Correlation With Overall Survival
Time Frame: Archival tissue samples were used for SPARC analysis. Survival was assessed for up to 38 months.

The expression and cellular distribution of Secreted Protein Acidic and Rich in cysteine (SPARC) in biopsies of lung tumor was examined by immunohistochemistry using a 2 antibody system by an approved central laboratory and analyzed by 2 pathologists. The following tissue components were scored: tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, and blood vessels.

To classify participants into "high-SPARC" and "low-SPARC" groups, an average z-score was calculated across variables and classified "high-SPARC" (average z-scores ≥0) and "low-SPARC" (average z-scores <0) groups.

SPARC status was then correlated with overall survival (the time from the day of randomization to participant death due to any cause).
Archival tissue samples were used for SPARC analysis. Survival was assessed for up to 38 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment, by Histology
Time Frame: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.

Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0.

A complete response was defined as a disappearance of all target and non-target lesions and no new lesions.

Partial response was defined as ≥ 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, and the persistence of one or more non-target lesions not qualifying for CR or Progressive Disease (the "unequivocal progression" of existing non-target lesion(s) or appearance of one or more new lesions).

Histology was determined at the time of primary diagnosis.
Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.
Maximal Degree of Anemia Based on Clinical Laboratory Values for Hemoglobin
Time Frame: 38 months
The maximal degree of anemia (and myelosuppression) was assessed by the overall nadir of hemoglobin levels based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
38 months
Maximal Degree of Neutropenia Based on Clinical Laboratory Values of Absolute Neutrophil Count
Time Frame: 38 months
The maximal degree of neutropenia (and myelosuppression) was assessed by the overall nadir of absolute neutrophil count (ANC) based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
38 months
Maximal Degree of Thrombocytopenia Based on Clinical Laboratory Values of Platelet Count
Time Frame: 38 months
The maximal degree of thrombocytopenia (and myelosuppression) was assessed by the overall nadir of platelet count based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
38 months
Time to Improvement of ≥ Grade 3 Treatment Related Peripheral Neuropathy
Time Frame: 38 months

Peripheral neuropathy was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death.

Improvement in peripheral neuropathy was evaluated as:

  • Time to improvement of grade 3 or higher peripheral neuropathy by at least one grade;
  • Time to improvement of grade 3 or higher peripheral neuropathy to grade 1.

Time to improvement was defined as the time from the first occurrence of grade 3 or higher treatment related neuropathy to improvement, as defined. Participants not experiencing improvement were censored at the last time the participant was evaluated for adverse events.
38 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Principal Investigator: Mark A Socinski, MD, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2007

Primary Completion (Actual)

October 1, 2009

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

October 4, 2007

First Submitted That Met QC Criteria

October 5, 2007

First Posted (Estimate)

October 8, 2007

Study Record Updates

Last Update Posted (Actual)

October 29, 2019

Last Update Submitted That Met QC Criteria

October 16, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA031

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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