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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00540514
First received: October 4, 2007
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

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).


Condition Intervention Phase
Non-Small Cell Lung Carcinoma
Drug: Albumin-bound paclitaxel
Drug: Paclitaxel
Drug: Carboplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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).



Secondary Outcome Measures:
  • Progression-free Survival by Blinded Radiology Assessment [ Time Frame: Assessed every 6 weeks until progression or death, up to 38 months ] [ Designated as safety issue: No ]

    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.


  • Overall Participant Survival [ Time Frame: Up to 38 months ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Controlled Disease [ Time Frame: Assessed every 6 weeks, up to 22 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Response in Responding Patients [ Time Frame: Assessed every 6 weeks, up to 38 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: Up to 38 months ] [ Designated as safety issue: Yes ]
    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.

  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

    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).



Other Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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.


  • Maximal Degree of Anemia Based on Clinical Laboratory Values for Hemoglobin [ Time Frame: 38 months ] [ Designated as safety issue: Yes ]
    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.

  • Maximal Degree of Neutropenia Based on Clinical Laboratory Values of Absolute Neutrophil Count [ Time Frame: 38 months ] [ Designated as safety issue: Yes ]
    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.

  • Maximal Degree of Thrombocytopenia Based on Clinical Laboratory Values of Platelet Count [ Time Frame: 38 months ] [ Designated as safety issue: Yes ]
    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.

  • Time to Improvement of ≥ Grade 3 Treatment Related Peripheral Neuropathy [ Time Frame: 38 months ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 1052
Study Start Date: November 2007
Study Completion Date: February 2013
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Paclitaxel
Administered by intravenous infusion.
Other Name: Taxol®
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00540514

  Show 37 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Principal Investigator: Mark A Socinski, MD University of North Carolina, Chapel Hill
  More Information

Publications:
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00540514     History of Changes
Other Study ID Numbers: CA031
Study First Received: October 4, 2007
Results First Received: June 7, 2013
Last Updated: August 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Advanced Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014