A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Advanced Nonsmall-Cell Lung Cancer
This study has been completed.
Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00723957
First received: July 25, 2008
Last updated: May 14, 2013
Last verified: May 2013
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced/Metastatic Non-Small Cell Lung Cancer |
Drug: Ixabepilone, 32 mg/m^2 Drug: Paclitaxel, 200 mg/m^2 Drug: Carboplatin (area under the concentration curve [AUC] 6) |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Patients With Advanced Non-small Cell Lung Cancer |
Resource links provided by NLM:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors [ Time Frame: Randomization to disease progression or death (maximum reached: 14.39 months ) ] [ Designated as safety issue: No ]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 [ Time Frame: Randomization to disease progression or death (maximum reached: 12.29 months) ] [ Designated as safety issue: No ]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 [ Time Frame: Randomization to disease progression or death, assessed to 12.29 months ] [ Designated as safety issue: No ]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) [ Time Frame: At randomization and then every 6 weeks to date of CR, PR, or progression for 6 21-day cycles ] [ Designated as safety issue: No ]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 Frame: Randomization to date of first response (PR or CR) ] [ Designated as safety issue: No ]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 [ Time Frame: Days 1 through 21, continuously ] [ Designated as safety issue: Yes ]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 [ Time Frame: At screening and weekly during 21-day cycle ] [ Designated as safety issue: Yes ]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 [ Time Frame: At screening and within 72 hours of start of 21-day cycle (Cycle 2 and beyond) ] [ Designated as safety issue: Yes ]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 [ Time Frame: Randomization to death ] [ Designated as safety issue: No ]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.
| Enrollment: | 260 |
| Study Start Date: | December 2008 |
| Study Completion Date: | August 2011 |
| Primary Completion Date: | May 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6) |
Drug: Ixabepilone, 32 mg/m^2
Intravenous (IV) solutions, ixabepilone, 32 mg/m^2
Other Names:
Drug: Carboplatin (area under the concentration curve [AUC] 6)
Carboplatin (AUC 6) day 1, every 21 days, 6 cycles
|
| Active Comparator: Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6) |
Drug: Paclitaxel, 200 mg/m^2
IV solutions, paclitaxel, 200 mg/m^2
Other Names:
Drug: Carboplatin (area under the concentration curve [AUC] 6)
Carboplatin (AUC 6) day 1, every 21 days, 6 cycles
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00723957
Show 33 Study Locations
Show 33 Study LocationsSponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00723957 History of Changes |
| Other Study ID Numbers: | CA163-163 |
| Study First Received: | July 25, 2008 |
| Results First Received: | June 20, 2011 |
| Last Updated: | May 14, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carboplatin |
Paclitaxel Epothilones Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic |
ClinicalTrials.gov processed this record on May 22, 2013