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:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00723957
First received: July 25, 2008
Last updated: May 22, 2013
Last verified: May 2013
  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 or last known alive date, up to 31.34 months ] [ 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:
  • IXEMPRA
  • BMS-247550
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:
  • TAXOL
  • BMS-181339
  • PARAPLATIN
  • BMY-26575
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723957

  Show 33 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 22, 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
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014