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Randomized Phase II Study of Ixabepilone Alone and Ixabepilone Plus Cetuximab as First-Line Treatment for Female Subjects With Triple Negative Locally Advanced Non-resectable and/or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00633464
First received: March 5, 2008
Last updated: May 9, 2012
Last verified: May 2012

March 5, 2008
May 9, 2012
June 2008
September 2010   (final data collection date for primary outcome measure)
  • Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST]) [ Time Frame: Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until disease progression (maximum participant objective response of 18.3 weeks) ] [ Designated as safety issue: No ]
    The participant had an OR if her best overall response (BOR) during the study was either a complete response (CR) or a partial response (PR) according to the RECIST as determined by the investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. Confidence interval (CI) was Computed using Clopper-Pearson method.
  • Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST) [ Time Frame: Assessed at 6 week intervals for first 12 months from randomization, thereafter every 3 months (to a maximum follow-up for tumor response of 17 months). ] [ Designated as safety issue: No ]
    PD = At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions.
Objective Response Rate [ Time Frame: The subject will have an OR if their best overall response during the study is either a Complete Response or a Partial Response according to the RECIST criteria ]
Complete list of historical versions of study NCT00633464 on ClinicalTrials.gov Archive Site
  • Progression Free Survival (PFS) [ Time Frame: From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 17 months) ] [ Designated as safety issue: No ]

    PFS is defined as the time interval from date of randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. The PFS was estimated using the Kaplan-Meier product-limit method, and a two-sided 95% CI for the median PFS time was computed using the method of Brookmeyer and Crowley.

    PD: At least 20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall.

  • Time to Response [ Time Frame: Assessed every 6 weeks for first 12 months from randomization thereafter every 3 months until CR or PR (maximum participant time to response of 18.3 weeks.) ] [ Designated as safety issue: No ]

    Time to response is defined as the time from the date of start of treatment until measurement criteria are first met for PR or CR (whichever is recorded first).

    CR: Disappearance of all target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all target lesions with reference to the baseline sum LD.

    Time to response was estimated using the Kaplan-Meier product-limit method.

  • Duration of Response [ Time Frame: From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 15.6 months) ] [ Designated as safety issue: No ]
    Defined as period from the time that measurement criteria are first met for CR or PR until first date of documented PD or death. Estimated using the Kaplan-Meier product-limit method; CI was computed using Brookmeyer and Crowley method. CR: Disappearance of all target and non-target lesions. PR: At least 30% reduction from baseline in the sum of LD of all target lesions with reference to baseline sum LD. PD: At least 20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall.
  • Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 [ Time Frame: Assessed from the date of first dose until at least 30 days after the last dose of study drug. Median time on ixapebilone therapy was 15 weeks (range: 3-54 weeks for ixabepilone arm; 3-36 weeks for ixabepilone+cetuximab arm) ] [ Designated as safety issue: Yes ]
    AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade (GR) 3=Severe; and GR4=Life-threatening or disabling. Other reasons for death included hepatic failure and respiratory distress.
  • Number of Participants With Hematology Abnormalities [ Time Frame: Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm) ] [ Designated as safety issue: Yes ]
    Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Hemoglobin:GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3:<8.0-6.5g/dL, GR4:<6.5g/dL. Platelets:GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3:<50.0-25.0*10^9/L, GR4:<25.0*10^9/L. Absolute Neutrophil Count (ANC):GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3:<1.0-0.5*10^9/L; GR4:<0.5*10^9/L. White blood cell (WBC):GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3:<2.0-1.0*10^9/L; GR4:<1.0*10^9/L. LLN=lower limit of normal.
  • Number of Participants With Serum Chemistry Abnormalities [ Time Frame: Assessed prior to 1st cycle, at beginning of each cycle, weekly (cetuximab treatment), and every 4 weeks within 30 days after last dose of study drug. Median time on ixapebilone therapy: 15 weeks (range:3-54:ixabepilone arm;3-36:ixapebilone+cetuximab arm) ] [ Designated as safety issue: Yes ]
    Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase: GR1=>ULN-2.5*ULN (upper limit of normal); GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4:>20.0*ULN. Total bilirubin:GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN.
  • Progression free survival [ Time Frame: The time in days from randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression ]
  • Time to response [ Time Frame: The time in days from first dosing until measurement criteria are first met for PR or CR (whichever is recorded first) ]
  • Duration of response [ Time Frame: the period measured in days from the time that measurement critiera are first met for CR or PR (whichever is recorded first) until the first date of documented progressive disease or death from any cause wihtout prior documentation of progression ]
Not Provided
Not Provided
 
Randomized Phase II Study of Ixabepilone Alone and Ixabepilone Plus Cetuximab as First-Line Treatment for Female Subjects With Triple Negative Locally Advanced Non-resectable and/or Metastatic Breast Cancer
Randomized Phase II Study of Ixabepilone Alone and Ixabepilone Plus Cetuximab as First-Line Treatment for Female Subjects With Triple Negative (ER, PR, Her2 Negative) Locally Advanced Non-resectable and/or Metastatic Breast Cancer

The purpose of this study was to estimate the response rate of ixabepilone monotherapy, and the combination of ixabepilone plus cetuximab as first-line treatment of female subjects with triple negative (estrogen receptor [ER], progesterone receptor [PR], Human Epidermal Growth Factor Receptor 2 [HER2] negative) locally advanced non-resectable and/or metastatic breast cancer

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Triple Negative Locally Advanced Non-resectable Breast Cancer
  • Metastatic Breast Cancer
  • Drug: ixabepilone

    injection, intravenous (IV), until unacceptable toxicity or progression or 15 months after the Last Subject First Visit (LSFV), whichever comes first.

    Ixabepilone 40 mg/m^2 was administered as a 3-hour IV continuous infusion on Day 1 in a 21-day cycle provided the participant met the re-treatment criteria.

    Other Names:
    • IXEMPRA
    • BMS-247550
  • Drug: ixabepilone + cetuximab

    Ixabepilone: injection, IV, until unacceptable toxicity or progression or 15 months after the LSFV, whichever comes first.

    Ixabepilone 40 mg/m^2 was administered as a 3-hour IV continuous infusion on Day 1 in a 21-day cycle provided the participant meets the re-treatment criteria.

    Cetuximab: injection, IV, until unacceptable toxicity or progression or 15 months after the LSFV, whichever comes first.

    Cetuximab 400 mg/m^2 was administered as a 2-hour IV loading dose via in-line filtration with an infusion pump, gravity drip, or a syringe pump on Day 1 of first cycle then 250 mg/m^2 1-hour IV once a week, i.e. on Days 1, 8, and 15 of each cycle provided the participant meets the re-treatment criteria.

    Other Names:
    • IXEMPRA
    • BMS-247550
    • ERBITUX
    • BMS-564717
  • Experimental: Arm A (ixabepilone 40 mg^2)
    ixabepilone 40 mg/m^2 every 3 weeks
    Intervention: Drug: ixabepilone
  • Experimental: Arm B (cetuximab 250 mg/m^2 + ixabepilone 40 mg/m^2)
    cetuximab 400 mg/m^2 loading dose then 250 mg/m^2 weekly + ixabepilone 40 mg/m^2 every 3 weeks
    Intervention: Drug: ixabepilone + cetuximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
79
May 2011
September 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Female subjects with triple negative (ER, PR, and HER2 negative) locally advanced non-resectable and/or metastatic breast cancer
  • Prior adjuvant or neoadjuvant anthracycline-based chemotherapy

Exclusion Criteria:

  • Tumors that are fluorescence in situ hybridization test (FISH) positive or immunohistochemistry (IHC) 3+
  • Neuropathy > Grade 1
  • Prior systemic therapy for metastatic disease
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Austria,   Czech Republic,   France,   Greece,   Italy,   Poland,   Spain
 
NCT00633464
CA163-139
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP