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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,052
Administered by intravenous infusion.
Administered by intravenous infusion.
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).
Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment
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).
Time frame: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.
Progression-free Survival by Blinded Radiology Assessment
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.
Time frame: Assessed every 6 weeks until progression or death, up to 38 months
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Clearview Cancer Institute Oncology Specialties, P.C.
Huntsville, Alabama, United States
Genesis Cancer Center- Hot Springs
Hot Springs, Arkansas, United States
Little Rock Hematology Oncology Associates
Little Rock, Arkansas, United States
Pacific Cancer Medical Center, Inc.
Anaheim, California, United States
Comprehensive Blood and Cancer Center
Bakersfield, California, United States
Southwest Cancer Care
Escondido, California, United States
Robert A. Moss, MD, FACP, Inc.
Fountain Valley, California, United States
Pacific Shores Medical Group
Long Beach, California, United States
Ventura County Hematology-Oncology Specialists
Oxnard, California, United States
Comprehensice Cancer Ctr.
Palms Springs, California, United States
...and 27 more locations
Overall Participant Survival
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.
Time frame: Up to 38 months
Percentage of Participants With Controlled Disease
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.
Time frame: Assessed every 6 weeks, up to 22 months
Duration of Response in Responding Patients
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.
Time frame: Assessed every 6 weeks, up to 38 months
Number of Participants With Adverse Events (AEs)
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.
Time frame: 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.
SPARC Status and Correlation With Overall Survival
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).
Time frame: Archival tissue samples were used for SPARC analysis. Survival was assessed for up to 38 months.