Advanced/Metastatic Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGIxabepilone, 32 mg/m^2
Intravenous (IV) solutions, ixabepilone, 32 mg/m\^2
DRUGPaclitaxel, 200 mg/m^2
IV solutions, paclitaxel, 200 mg/m\^2
DRUGCarboplatin (area under the concentration curve [AUC] 6)
Carboplatin (AUC 6) day 1, every 21 days, 6 cycles
Sponsors
R-Pharm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors | Randomization to disease progression or death (maximum reached: 14.39 months ) | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival in the Overall Population | Randomization to disease progression or death, assessed to 12.29 months | 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) | At randomization and then every 6 weeks to date of CR, PR, or progression for 6 21-day cycles | 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 | Randomization to date of first response (PR or CR) | Time to Response is defined as the time from randomization date until the date of first response (Partial Response \[PR\] or Complete Response \[CR\]) |
| Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors | Randomization to disease progression or death (maximum reached: 12.29 months) | 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. |
| Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | At screening and weekly during 21-day cycle | 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 | At screening and within 72 hours of start of 21-day cycle (Cycle 2 and beyond) | 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 | Randomization to death or last known alive date, up to 31.34 months | 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. |
| 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 | Days 1 through 21, continuously | 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. |
Countries
Argentina, Australia, France, Germany, Italy, Russia, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
Of 260 participants enrolled, 197 were randomized. Among those randomized, 191 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) Ixabepilone administered as a 3-hour intravenous (IV) infusion at a starting dose of 32 mg/m\^2 on Day 1 of a 21-day cycle followed by carboplatin, administered at a dose calculated to produce an area under the concentration-time curve (AUC) of 6 mg/mL per minute (AUC 6), on Day 1 of a 21-day cycle for a maximum of 6 cycles | 98 |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) Paclitaxel administered as a 3-hour IV infusion at a starting dose of 200 mg/m\^2 on Day 1 of a 21-day cycle followed by carboplatin, administered at a dose calculated to produce an AUC 6, on Day 1 of a 21-day cycle for a maximum of 6 cycles | 99 |
| Total | 197 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 1 | 4 |
| Overall Study | Death | 3 | 4 |
| Overall Study | Disease progression | 27 | 25 |
| Overall Study | Investigator decision | 1 | 1 |
| Overall Study | Maximum clinical benefit | 4 | 5 |
| Overall Study | Never received treatment | 3 | 3 |
| Overall Study | Reason not analyzed | 1 | 0 |
| Overall Study | Study drug toxicity | 4 | 6 |
| Overall Study | Withdrawal by Subject | 7 | 5 |
Baseline characteristics
| Characteristic | Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Total |
|---|---|---|---|
| Age, Customized Beta III (βIII)-tubulin positive tumors (n=53, 51) | 60.0 Years | 60.0 Years | 60.0 Years |
| Age, Customized βIII-tubulin negative tumors (N=45, 48) | 60.0 Years | 60.5 Years | 60.0 Years |
| Number of participants with βIII-tubulin positive and negative tumors βIII tubulin-negative tumors | 45 Participants | 48 Participants | 93 Participants |
| Number of participants with βIII-tubulin positive and negative tumors βIII tubulin-positive tumors | 53 Participants | 51 Participants | 104 Participants |
| Race/Ethnicity, Customized Asian | 30 participants | 22 participants | 52 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 68 participants | 76 participants | 144 participants |
| Sex: Female, Male Female | 72 Participants | 67 Participants | 139 Participants |
| Sex: Female, Male Male | 26 Participants | 32 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 88 / 95 | 91 / 96 |
| serious Total, serious adverse events | 27 / 95 | 28 / 96 |
Outcome results
Primary
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.
Time frame: Randomization to disease progression or death (maximum reached: 14.39 months )
Population: All randomized participants with βIII-tubulin positive tumors and who received study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors | 4.27 Months |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors | 4.27 Months |
Regression, Cox
Comparison: P-value is 1-sidedp-value: 0.5735Log Rank
Secondary
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.
Time frame: Randomization to death or last known alive date, up to 31.34 months
Population: All participants randomized to receive treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | βIII-tubulin positive subgroup (n=53, 51) | 10.61 Months |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | βIII-tubulin negative subgroup (n=45, 48) | 16.92 Months |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 population | 13.04 Months |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | βIII-tubulin positive subgroup (n=53, 51) | 11.37 Months |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | βIII-tubulin negative subgroup (n=45, 48) | 9.40 Months |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 population | 10.15 Months |
Regression, Cox
Regression, Cox
Regression, Cox
Secondary
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.
Time frame: Days 1 through 21, continuously
Population: All participants who received any investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | Death | 28 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | Drug-related AEs | 85 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | SAEs | 27 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | Drug-related SAEs | 15 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | AEs Leading to Discontinuation | 11 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | 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 | Drug-related peripheral neuropathy | 35 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | AEs Leading to Discontinuation | 15 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | Death | 34 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | Drug-related SAEs | 9 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | Drug-related AEs | 87 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | Drug-related peripheral neuropathy | 54 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | 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 | SAEs | 28 Participants |
Secondary
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
Time frame: At screening and within 72 hours of start of 21-day cycle (Cycle 2 and beyond)
Population: All participants who received any investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | ALP, Grade 3 | 1 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | ALP. Grade 4 | 0 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | AST, Grade 3 | 0 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | AST, Grade 4 | 0 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | AST, Grade 4 | 0 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | ALP, Grade 3 | 0 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | AST, Grade 3 | 1 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results | ALP. Grade 4 | 0 Participants |
Secondary
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.
Time frame: At screening and weekly during 21-day cycle
Population: All participants who received any investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Leukopenia, Grade 3 or 4 | 31 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Neutropenia, Grade 3 or 4 | 54 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Thrombocytopenia, Grade 3 or 4 | 14 Participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Anemia, Grade 3 or 4 | 15 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Anemia, Grade 3 or 4 | 0 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Leukopenia, Grade 3 or 4 | 15 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Thrombocytopenia, Grade 3 or 4 | 1 Participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Number of Participants With Hematology Laboratory Results of Grade 3 or 4 | Neutropenia, Grade 3 or 4 | 51 Participants |
Secondary
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 frame: At randomization and then every 6 weeks to date of CR, PR, or progression for 6 21-day cycles
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) | βIII-tubulin positive subgroup (n=53, n=51) | 17.0 Percentage of participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) | βIII-tubulin negative subgroup (n=45, n=48) | 26.7 Percentage of participants |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) | Overall population | 21.4 Percentage of participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) | βIII-tubulin positive subgroup (n=53, n=51) | 29.4 Percentage of participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) | βIII-tubulin negative subgroup (n=45, n=48) | 27.1 Percentage of participants |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) | Overall population | 28.3 Percentage of participants |
Secondary
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.
Time frame: Randomization to disease progression or death, assessed to 12.29 months
Population: All randomized participants who received study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Progression-free Survival in the Overall Population | 5.29 Months |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Progression-free Survival in the Overall Population | 5.13 Months |
Regression, Cox
Comparison: P-value is 1-sidedp-value: 0.316Log Rank
Secondary
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.
Time frame: Randomization to disease progression or death (maximum reached: 12.29 months)
Population: All randomized participants who had βIII-tubulin positive tumors and who received study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors | 5.78 Months |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors | 5.32 Months |
Regression, Cox
Comparison: P-value is 1-sidedp-value: 0.175Log Rank
Secondary
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 \[CR\])
Time frame: Randomization to date of first response (PR or CR)
Population: All randomized participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Time to Response | Beta III positive (n=9, 15) | 12.1 Weeks |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Time to Response | Beta III negative (n=12, 13) | 9.5 Weeks |
| Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) | Time to Response | Overall population | 12.1 Weeks |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Time to Response | Beta III positive (n=9, 15) | 6.6 Weeks |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Time to Response | Beta III negative (n=12, 13) | 7.0 Weeks |
| Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) | Time to Response | Overall population | 6.6 Weeks |