A Study Comparing Eribulin Mesylate and Ixabepilone in Causing or Exacerbating Neuropathy in Participants With Advanced Breast Cancer
- Registration Number
- NCT00879086
- Lead Sponsor
- Eisai Inc.
- Brief Summary
The purpose of this study in patients with advanced breast cancer is to compare the incidence and severity of neuropathy adverse events for the two treatment groups (eribulin versus ixabepilone) using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) grading.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 104
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eribulin mesylate Eribulin Mesylate - Ixabepilone Ixabepilone -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-Emergent Neuropathy Adverse Events (AEs) From administration of first dose up to approximately 5 years Neuropathy AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and coded according to the current version of the Medical Dictionary for Regulatory Activities (MedDRA). Neuropathy AEs included the broad list of preferred terms (PTs) defined in the Standard MedDRA Query for Neuropathy and the following additional PTs: neuropathy, hyperesthesia, painful response to normal stimuli, pallanesthesia, and allodynia. If the post-baseline maximum CTCAE grade of the combined term "neuropathy" was greater than the baseline maximum CTCAE grade of the combined term, then the event was considered as treatment emergent neuropathy adverse events per CTCAE grade. For a single participant, 1) a neuropathy AE occurring more than once during the study, whether defined with the same or different MedDRA PTs, was counted only once, 2) a neuropathy AE with different CTCAE grades had only the highest grade AE counted.
- Secondary Outcome Measures
Name Time Method Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 2 (Motor) Baseline up to approximately 5 years The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Motor scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were motor were evaluated with the PNQ Item 2 (motor). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Eribulin and Ixabepilone For each participant, from the first dose till 42 days after the last dose of study treatment (Up to approximately 5 years) General safety was assessed by monitoring all TEAEs and SAEs. TEAEs were reported at a frequency of 0% or greater in the study population.
Percentage of Participants With an Incidence of Treatment-emergent Myalgia/Arthralgia From administration of first dose up to approximately 5 years The incidence rate of TE myalgia/arthralgia was calculated as the percent of participants with TE myalgia/arthralgia. A participant who had an arthralgia or myalgia AE more than once over the course of the study was counted only once in the incidence calculation for myalgia/arthralgia AEs. A participant who had myalgia/arthralgia AEs with different CTCAE grades was counted with the highest CTCAE grade over the course of the evaluation period. If the post-baseline CTCAE grade of the combined term "Myalgia/Arthralgia" was greater than the baseline maximum CTCAE grade of the combined term, the participant had TE myalgia/arthralgia. The 2-sided 95% confidence interval (CI) for incidence rate of TE myalgia/arthralgia was calculated using the Clopper-Pearson method (i.e., the exact method) for each treatment group.
Change From Baseline in Vibration Perception Threshold (VPT) Baseline, Treatment Phase: Cycles 2 to 6 (Day 1); Extension Phase: Cycle 9 Day 1, Cycle 12 Day 1, Cycle 15 Day 1 (Each Cycle length=21 days), End of Treatment, Post-treatment Follow-up, Worst Post-baseline result (Up to approximately 5 years) The participant-reported questionnaire was used to compare the incidence and severity of neuropathy AEs. Sensory and motor scores were to be analyzed separately using a generalized linear model. Separate subgroup analyses were performed by each stratification variable. VPAT was measured using a Vibratron II device (Physitemp, Inc.) and a modified Two Alternative Forced Choice psychophysical algorithm. VPT was assessed on the ventral surface of the distal index finger (side opposite the nail), contralateral to the side of the mastectomy or primary disease and on the distal fleshy pad of both the right and left great toes (side opposite the nail). If the mastectomy was bilateral, the index finger on the side without axillary lymph node dissection was tested. Data ranged from 0 (invalid) to 20 vu. A lower VPT indicated a greater sensitivity.
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Composite Score Baseline up to approximately 5 years The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. Sensory scores, motor scores and composite scores were analyzed separately. For both item 1 and item 2, letter scores (A=none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A(none)=0, B(mild)=1, C(moderate)=2, D(moderate to severe)=3 and E (severe)=4. Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. PNQ composite score was defined as the worst of Item 1 and Item 2 score. If neither Item 1 or item 2 score was D or E, but if a box was checked in Item 3, PNQ composite score would be D. Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.
Number of Participants With Shift From Baseline to Worst Post-baseline Participant Neurotoxicity Questionnaire (PNQ) Score for Item 1 (Sensory) Baseline up to approximately 5 years The PNQ consisted of 3 parts; Item 1 (sensory) measured numbness, pain, burning or tingling in hands or feet, Item 2 (motor) measured weakness in arms or legs, and Item 3 (activities) measured activities that interfered with daily life. The participant was told that there was no right or wrong answer and their answer should reflect how they currently felt since last completing the PNQ. Sensory scores were analyzed separately. Letter scores (A= none, B=mild, C=moderate, D=moderate to severe, and E=severe) for PNQ were converted to numeric scores A (none)=0, B (mild)=1, C (moderate)=2, D (moderate to severe)=3 and E (severe)=4). Total scores ranged from 0 (minimum severity) to 10 (maximum severity). Higher scores indicated greater severity. Neuropathy AEs that were sensory were evaluated with the PNQ Item 1 (sensory). Categories where no participant showed any shift from baseline to post-baseline for both the arms were not included in the presentation.
Objective Response Rate (ORR) From date of treatment start until disease progression (PD) (Up to approximately 5 years) ORR was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 for target lesions assessed by magnetic resonance imaging and computed tomography and investigator assessment. Participants with unknown or missing responses were treated as non-responders. CR was defined as disappearance of all target lesions. PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper-Pearson method for calculating the exact binomial intervals.
Duration of Response (DoR) From date of first CR or PR until the first documentation of PD or date of death (Up to approximately 5 years) DoR was defined as the time from first documented CR or PR until PD or death from any cause. It was measured from the time that measurement criteria were met for CR or PR (whichever status was recorded first) until the first date that recurrent or PD was objectively documented. It was defined for participants with a confirmed CR or a confirmed PR. Participants without progressive disease or death were censored. Median duration and 95% CI of the median were estimated for each treatment group, using the Kaplan-Meier method.
Progression-Free Survival (PFS) From date of treatment start until the date of PD or death from any cause (Up to approximately 5 years) PFS was defined as the time from randomization until PD or death due to any cause as determined by the investigator. Disease progression per RECIST v1.0 was defined as at least a 20% relative increase and 5 millimeter absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. The duration of PFS was calculated as the end date minus date of first drug plus 1. For participants who did not have an event (those lost to follow-up or who had not progressed at the date of data cut-off) PFS was censored. The median PFS and corresponding 95% CI was estimated for each treatment group using the Kaplan-Meier method.
Clinical Benefit Rate (CBR) From date of treatment start until PD or death from any cause, whichever occurred first (Up to approximately 5 years) CBR was defined as the number of participants (CR + PR + stable disease (SD) greater than or equal to 6 months) divided by the number of participants in the analysis population. The 95% CI was generated for the clinical benefit rate for each treatment group, and it was based on the Clopper-Pearson method for calculating the exact binomial intervals.
Trial Locations
- Locations (47)
Northwest Cancer Center
🇺🇸Corpus Christi, Texas, United States
Texas Oncology-Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
Central Indiana Cancer Centers
🇺🇸Indianapolis, Indiana, United States
Texas Oncology, PA Bedford
🇺🇸Houston, Texas, United States
Northern AZ Hematology and Oncology Associates
🇺🇸Sedona, Arizona, United States
Comprehensive Cancer Center
🇺🇸Palm Springs, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Hematology Oncology Associates of Illinois
🇺🇸Chicago, Illinois, United States
Healing Hands Oncology and Medical Care
🇺🇸Hawthorne, California, United States
Comprehensive Cancer Care Specialist of Boca
🇺🇸Boca Raton, Florida, United States
Oncology and Hematology Associates of West Broward
🇺🇸Tamarac, Florida, United States
Queens Cancer Center of Queens Hospital
🇺🇸Jamaica, New York, United States
Hematology and Oncology Specialists
🇺🇸New Orleans, Louisiana, United States
Washington County Hospital
🇺🇸Hagerstown, Maryland, United States
Joan Knechel Cancer Center
🇺🇸Mount Arlington, New Jersey, United States
Henry Ford Health Systems
🇺🇸Detroit, Michigan, United States
Maryland Oncology Hematology, PA
🇺🇸Columbia, Maryland, United States
Henry Ford Medical Center-Fairlane
🇺🇸Dearborn, Michigan, United States
Henry Ford Medical Center Farmington
🇺🇸West Bloomfield, Michigan, United States
Summit Medical Group
🇺🇸Berkeley Heights, New Jersey, United States
Northwest Cancer Specialists Hoyt
🇺🇸Portland, Oregon, United States
Weil Cornell Breast Center
🇺🇸New York, New York, United States
Cancer Center of North Carolina
🇺🇸Raleigh, North Carolina, United States
Charleston Hematology Oncology Associates PA
🇺🇸Charleston, North Carolina, United States
Texas Cancer Center at Medical City
🇺🇸Dallas, Texas, United States
Texas Oncology, PA
🇺🇸Houston, Texas, United States
Northwest Cancer Specialist Vancouver
🇺🇸Vancouver, Washington, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Robert R. Carroll, MD, PA
🇺🇸Gainesville, Florida, United States
Hematology Oncology Associates
🇺🇸Lake Worth, Florida, United States
Medical Specialists of the Palm Beaches
🇺🇸Lake Worth, Florida, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Hematology Oncology Associates of Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Metairie Institute of Comprehensive Health
🇺🇸Metairie, Louisiana, United States
Saint Vincent's Comprehensive Cancer Center
🇺🇸New York, New York, United States
Northwest Cancer Specialists
🇺🇸Tualatin, Oregon, United States
South Texas Institute of Cancer
🇺🇸Corpus Christi, Texas, United States
Lone Star Oncology
🇺🇸Austin, Texas, United States
North Texas Regional Cancer Center
🇺🇸Plano, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
Northwest Cancer Care Specialists, P.C.
🇺🇸Vancouver, Washington, United States
Josephine Ford Cancer Center
🇺🇸Brownstown, Michigan, United States
Heartland Oncology Hematology
🇺🇸Council Bluffs, Iowa, United States
Northwest Cancer Specialists Rose Quarter
🇺🇸Portland, Oregon, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States