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
  Purpose

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


Condition Intervention Phase
Triple Negative Locally Advanced Non-resectable Breast Cancer
Metastatic Breast Cancer
Drug: ixabepilone
Drug: ixabepilone + cetuximab
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: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 79
Study Start Date: June 2008
Study Completion Date: May 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (ixabepilone 40 mg^2)
ixabepilone 40 mg/m^2 every 3 weeks
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
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00633464

Locations
Austria
Local Institution
Graz, Austria, 8036
Local Institution
Wien, Austria, 1090
Czech Republic
Local Institution
Brno, Czech Republic, 656 53
Local Institution
Prague 5, Czech Republic, 150 06
Local Institution
Praha 2, Czech Republic, 128 08
France
Local Institution
Bayonne, France, 64100
Local Institution
Dijon Cedex, France, 21079
Local Institution
Lyon, France, 69008
Local Institution
Paris Cedex 13, France, 75651
Local Institution
Saint Brieuc, France, 22015
Local Institution
Saint Herblain Cedex, France, 44805
Local Institution
Toulouse Cedex, France, 31052
Greece
Local Institution
Thessaloniki, Greece, 54642
Italy
Local Institution
Napoli, Italy, 80131
Poland
Local Institution
Gdansk, Poland, 80952
Local Institution
Olsztyn, Poland, 10-513
Spain
Local Institution
Barcelona, Spain, 08036
Local Institution
Barcelona, Spain, 08221
Local Institution
Barcelona, Spain, 08208
Sponsors 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: NCT00633464     History of Changes
Other Study ID Numbers: CA163-139
Study First Received: March 5, 2008
Results First Received: March 30, 2012
Last Updated: May 9, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Epothilones
Cetuximab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014