Back to resultsA Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Advanced Nonsmall-Cell Lung Cancer
Primary Purpose
Advanced/Metastatic Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ixabepilone, 32 mg/m^2
Paclitaxel, 200 mg/m^2
Carboplatin (area under the concentration curve [AUC] 6)
Sponsored by
About this trial
This is an interventional treatment trial for Advanced/Metastatic Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed non-small cell lung cancer (NSCLC)(squamous cell, adenocarcinoma, large cell, or bronchoalveolar carcinoma)
- Stage IIIB NSCLC with pleural effusion, Stage IV NSCLC, or recurrent disease following surgery with or without radiation therapy
- Available paraffin-embedded tissue to measure the expression levels of βIII tubulin
- Disease measurable by Response Evaluation Criteria in Solid Tumors, with at least 1 target lesion situated outside any previous radiotherapy field
- Karnofsky performance status of 70-100
- Life expectancy of at least 3 months
- Men and women, ages 18 years and older
Exclusion Criteria:
- Uncontrolled brain metastases
- Peripheral neuropathy greater than Grade 1
- Fewer than 4 weeks from prior radiation therapy or locoregional surgeries to randomization date (less than 1 week from focal/palliative radiotherapy or minor surgery)
- Any concurrent malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix
- Known HIV-positive status
- Absolute neutrophil count lower than 1500 cells mm^3
- Total bilirubin level higher than upper limit of normal (ULN) as defined by the institution (with the exception of elevation due to Gilbert's syndrome)
- Aspartate transaminase or alanine transaminase level higher than 2.5*ULN
- Serum creatine level of 1.5 mg/dL or higher
- Renal function with a creatinine clearance of less than 50 mL/min (as calculated with the Cockcroft and Gault equation)
- Any prior antineoplastic systemic regimens.
Sites / Locations
- Scripps Cancer Center
- Uof Md,Greenebaum Cancer Ctr.
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)
Arm Description
Outcomes
Primary Outcome Measures
Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors
Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on-study tumor assessment, progression-free survival was censored at the date of randomization. A tumor was considered to be beta III (βIII)-tubulin positive if 50% or more of the tumor cells had a βIII-tubulin immunohistochemistry staining intensity equal to or greater than that of the positive control.
Secondary Outcome Measures
Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors
Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on study tumor assessment, progression-free survival was censored at the date of randomization.
Progression-free Survival in the Overall Population
Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on study tumor assessment, progression-free survival was censored at the date of randomization.
Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR)
Response evaluated per Response Evaluaton in Solid Tumor (V1.0) guidelines and assessed using magnetic resonance imaging. Percentage of best response=the total number of participants with the best overall response of CR or PR divided by the total number of randomized participants in that treatment arm. CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time to Response
Time to Response is defined as the time from randomization date until the date of first response (Partial Response [PR] or Complete Response [CR])
Number of Participants With Death as Outcome, Drug-related Adverse Events (AEs), Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation, and Drug-related Peripheral Neuropathy
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related is defined as possibly, probably, or certainly related to and of unknown relationship to study treatment.
Number of Participants With Hematology Laboratory Results of Grade 3 or 4
LLN=lower level of normal. Leukocytes (leukopenia) Grade 1: <LLN to 3.0*10^9/L, Grade 2:<3.0 to 2.0*10^9/L, Grade 3: <2.0 to 1.0*10^9/L, Grade 4: <1.0*10^9/L; Neutrophils (neutropenia) Grade 1: <LLN to 1.5*10^9/L, Grade 2: <1.5 to 1.0*10^9/L, Grade 3: <1.0 to 0.5*10^9/L, Grade 4: <0.5*10^9/L; Platelet count(thrombocytopenia) Grade 1: LLN to 75.0*10^9/L, Grade 2: <75.0 to 50.0*10^9/L, Grade 3: <50.0 to 25.0*10^9/L, Grade 4:<25.0 to 10^9/L; Hemoglobin (anemia) Grade 1: <LLN to 10.0 g/dL, Grade 2: <10.0 to 8.0 g/dL, Grade 3: <8.0 to 6.5 g/dL, Grade 4: <6.5 g/dL.
Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results
ULN=upper level of normal. Alkaline phosphatase (ALP) Gr 1:>ULN to 2.5*ULN, Gr 2: >2.5 to 5.0*ULN, Gr 3: >5.0 to 20.0*ULN, Gr 4: >20.0*ULN; Aspartate aminotransferase (AST) Gr 1: >ULN to 2.5*ULN, Gr 2: >2.5 to 5.0*ULN, Gr 3: >5.0 to 20.0*ULN, Gr 4: >20.0*ULN
Median Length of Survival in the Overall Population and in the Subgroups of Patients With βIII-tubulin Positive (β3T+) and βIII-tubulin Negative (β3T-)Tumors
Overall Survival was computed for all randomized participants and was defined as the time between randomization and death. Participants who did not die at the end of the study were censored at their last known alive date.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00723957
Brief Title
A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Advanced Nonsmall-Cell Lung Cancer
Official Title
A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Patients With Advanced Non-small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
R-Pharm
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether progression-free survival with ixabepilone is superior to that achieved with paclitaxel plus carboplatin in participants with advanced nonsmall-cell lung cancer and beta III (βIII)-tubulin-positive tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced/Metastatic Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
260 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)
Arm Type
Experimental
Arm Title
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Ixabepilone, 32 mg/m^2
Other Intervention Name(s)
IXEMPRA, BMS-247550
Intervention Description
Intravenous (IV) solutions, ixabepilone, 32 mg/m^2
Intervention Type
Drug
Intervention Name(s)
Paclitaxel, 200 mg/m^2
Other Intervention Name(s)
TAXOL, BMS-181339, PARAPLATIN, BMY-26575
Intervention Description
IV solutions, paclitaxel, 200 mg/m^2
Intervention Type
Drug
Intervention Name(s)
Carboplatin (area under the concentration curve [AUC] 6)
Intervention Description
Carboplatin (AUC 6) day 1, every 21 days, 6 cycles
Primary Outcome Measure Information:
Title
Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors
Description
Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on-study tumor assessment, progression-free survival was censored at the date of randomization. A tumor was considered to be beta III (βIII)-tubulin positive if 50% or more of the tumor cells had a βIII-tubulin immunohistochemistry staining intensity equal to or greater than that of the positive control.
Time Frame
Randomization to disease progression or death (maximum reached: 14.39 months )
Secondary Outcome Measure Information:
Title
Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors
Description
Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on study tumor assessment, progression-free survival was censored at the date of randomization.
Time Frame
Randomization to disease progression or death (maximum reached: 12.29 months)
Title
Progression-free Survival in the Overall Population
Description
Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on study tumor assessment, progression-free survival was censored at the date of randomization.
Time Frame
Randomization to disease progression or death, assessed to 12.29 months
Title
Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR)
Description
Response evaluated per Response Evaluaton in Solid Tumor (V1.0) guidelines and assessed using magnetic resonance imaging. Percentage of best response=the total number of participants with the best overall response of CR or PR divided by the total number of randomized participants in that treatment arm. CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time Frame
At randomization and then every 6 weeks to date of CR, PR, or progression for 6 21-day cycles
Title
Time to Response
Description
Time to Response is defined as the time from randomization date until the date of first response (Partial Response [PR] or Complete Response [CR])
Time Frame
Randomization to date of first response (PR or CR)
Title
Number of Participants With Death as Outcome, Drug-related Adverse Events (AEs), Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation, and Drug-related Peripheral Neuropathy
Description
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related is defined as possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time Frame
Days 1 through 21, continuously
Title
Number of Participants With Hematology Laboratory Results of Grade 3 or 4
Description
LLN=lower level of normal. Leukocytes (leukopenia) Grade 1: <LLN to 3.0*10^9/L, Grade 2:<3.0 to 2.0*10^9/L, Grade 3: <2.0 to 1.0*10^9/L, Grade 4: <1.0*10^9/L; Neutrophils (neutropenia) Grade 1: <LLN to 1.5*10^9/L, Grade 2: <1.5 to 1.0*10^9/L, Grade 3: <1.0 to 0.5*10^9/L, Grade 4: <0.5*10^9/L; Platelet count(thrombocytopenia) Grade 1: LLN to 75.0*10^9/L, Grade 2: <75.0 to 50.0*10^9/L, Grade 3: <50.0 to 25.0*10^9/L, Grade 4:<25.0 to 10^9/L; Hemoglobin (anemia) Grade 1: <LLN to 10.0 g/dL, Grade 2: <10.0 to 8.0 g/dL, Grade 3: <8.0 to 6.5 g/dL, Grade 4: <6.5 g/dL.
Time Frame
At screening and weekly during 21-day cycle
Title
Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results
Description
ULN=upper level of normal. Alkaline phosphatase (ALP) Gr 1:>ULN to 2.5*ULN, Gr 2: >2.5 to 5.0*ULN, Gr 3: >5.0 to 20.0*ULN, Gr 4: >20.0*ULN; Aspartate aminotransferase (AST) Gr 1: >ULN to 2.5*ULN, Gr 2: >2.5 to 5.0*ULN, Gr 3: >5.0 to 20.0*ULN, Gr 4: >20.0*ULN
Time Frame
At screening and within 72 hours of start of 21-day cycle (Cycle 2 and beyond)
Title
Median Length of Survival in the Overall Population and in the Subgroups of Patients With βIII-tubulin Positive (β3T+) and βIII-tubulin Negative (β3T-)Tumors
Description
Overall Survival was computed for all randomized participants and was defined as the time between randomization and death. Participants who did not die at the end of the study were censored at their last known alive date.
Time Frame
Randomization to death or last known alive date, up to 31.34 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed non-small cell lung cancer (NSCLC)(squamous cell, adenocarcinoma, large cell, or bronchoalveolar carcinoma)
Stage IIIB NSCLC with pleural effusion, Stage IV NSCLC, or recurrent disease following surgery with or without radiation therapy
Available paraffin-embedded tissue to measure the expression levels of βIII tubulin
Disease measurable by Response Evaluation Criteria in Solid Tumors, with at least 1 target lesion situated outside any previous radiotherapy field
Karnofsky performance status of 70-100
Life expectancy of at least 3 months
Men and women, ages 18 years and older
Exclusion Criteria:
Uncontrolled brain metastases
Peripheral neuropathy greater than Grade 1
Fewer than 4 weeks from prior radiation therapy or locoregional surgeries to randomization date (less than 1 week from focal/palliative radiotherapy or minor surgery)
Any concurrent malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix
Known HIV-positive status
Absolute neutrophil count lower than 1500 cells mm^3
Total bilirubin level higher than upper limit of normal (ULN) as defined by the institution (with the exception of elevation due to Gilbert's syndrome)
Aspartate transaminase or alanine transaminase level higher than 2.5*ULN
Serum creatine level of 1.5 mg/dL or higher
Renal function with a creatinine clearance of less than 50 mL/min (as calculated with the Cockcroft and Gault equation)
Any prior antineoplastic systemic regimens.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Scripps Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
90237
Country
United States
Facility Name
Uof Md,Greenebaum Cancer Ctr.
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Local Institution
City
Capital Federal
State/Province
Buenos Aires
ZIP/Postal Code
1425
Country
Argentina
Facility Name
Local Institution
City
Capital Federal
State/Province
Buenos Aires
ZIP/Postal Code
1437
Country
Argentina
Facility Name
Local Institution
City
Buenos Aires
ZIP/Postal Code
C1426ANZ
Country
Argentina
Facility Name
Local Institution
City
Bankstown
State/Province
New South Wales
ZIP/Postal Code
2200
Country
Australia
Facility Name
Local Institution
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Facility Name
Local Institution
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Local Institution
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Local Institution
City
Strasbourg
ZIP/Postal Code
67085
Country
France
Facility Name
Local Institution
City
Strasbourg
ZIP/Postal Code
67090
Country
France
Facility Name
Local Institution
City
Bad Berka
ZIP/Postal Code
99437
Country
Germany
Facility Name
Local Institution
City
Grosshansdorf
ZIP/Postal Code
22927
Country
Germany
Facility Name
Local Institution
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Local Institution
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Local Institution
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Local Institution
City
Sondrio
ZIP/Postal Code
23100
Country
Italy
Facility Name
Local Institution
City
Terni
ZIP/Postal Code
05100
Country
Italy
Facility Name
Local Institution
City
Goyang-Si
State/Province
Gyeonggi-Do
ZIP/Postal Code
411-769
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Local Institution
City
Chelyabinsk
ZIP/Postal Code
454087
Country
Russian Federation
Facility Name
Local Institution
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
Local Institution
City
Moscow
ZIP/Postal Code
115 478
Country
Russian Federation
Facility Name
Local Institution
City
Moscow
ZIP/Postal Code
129128
Country
Russian Federation
Facility Name
Local Institution
City
Ryazan
ZIP/Postal Code
390011
Country
Russian Federation
Facility Name
Local Institution
City
St. Petersburg
ZIP/Postal Code
194291
Country
Russian Federation
Facility Name
Local Institution
City
St. Petersburg
ZIP/Postal Code
198255
Country
Russian Federation
Facility Name
Local Institution
City
Baracaldo (Vizcaya)
ZIP/Postal Code
48903
Country
Spain
Facility Name
Local Institution
City
Taichung
ZIP/Postal Code
407.5
Country
Taiwan
Facility Name
Local Institution
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
Facility Name
Local Institution
City
Taoyuan Hsien
ZIP/Postal Code
333
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
23589560
Citation
Edelman MJ, Schneider CP, Tsai CM, Kim HT, Quoix E, Luft AV, Kaleta R, Mukhopadhyay P, Trifan OC, Whitaker L, Reck M. Randomized phase II study of ixabepilone or paclitaxel plus carboplatin in patients with non-small-cell lung cancer prospectively stratified by beta-3 tubulin status. J Clin Oncol. 2013 Jun 1;31(16):1990-6. doi: 10.1200/JCO.2012.45.3282. Epub 2013 Apr 15.
Results Reference
derived
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A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Advanced Nonsmall-Cell Lung Cancer
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