- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00490646
A Phase II Combination of Trastuzumab and Ixabepilone Versus Trastuzumab and Docetaxel in Patients With Advanced and/or Metastatic Breast Cancer
Randomized Phase II Study of Ixabepilone Plus Trastuzumab vs. Docetaxel Plus Trastuzumab in Female Subjects With Her2+ Locally Advanced and/or Metastatic Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Caen, France, F-14076
- Local Institution
-
Grenoble, France, 38028
- Local Institution
-
St Priest En Jarez, France, 42271
- Local Institution
-
Toulouse, France, 31300
- Local Institution
-
-
-
-
-
Athens, Greece, 11522
- Local Institution
-
Athens, Greece, 12462
- Local Institution
-
Pireaus, Greece, 18537
- Local Institution
-
-
-
-
-
Bologna, Italy, 40138
- Local Institution
-
Brescia, Italy, 25123
- Local Institution
-
Modena, Italy, 41100
- Local Institution
-
Napoli, Italy, 80131
- Local Institution
-
Roma, Italy, 00144
- Local Institution
-
Sora, Italy, 03039
- Local Institution
-
-
-
-
-
Madrid, Spain, 28034
- Local Institution
-
Madrid, Spain, 28007
- Local Institution
-
-
-
-
-
Ankara, Turkey, 06100
- Local Institution
-
Ankara, Turkey, 06500
- Local Institution
-
Izmir, Turkey, 35100
- Local Institution
-
Izmir, Turkey, 35340
- Local Institution
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Locally advanced or metastatic HER2+ breast cancer not previously treated with chemotherapy or trastuzumab.
- Subjects who had received prior (neo)adjuvant chemotherapy or trastuzumab were eligible except if they relapsed within 12 months after the last dose of a taxane or trastuzumab given as (neo)adjuvant therapy.
- Measurable disease
- Left Ventricular Ejection Fraction (LVEF) ≥50%
Exclusion Criteria:
- Prior chemotherapy or trastuzumab for metastatic breast cancer (MBC)
- Relapse within 1 year after (neo)adjuvant taxane or trastuzumab
- Neuropathy > Grade 1
- Significant cardiovascular disease
- Any brain metastases
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A
trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + ixabepilone 40 mg/m^2 intravenous (IV) over 3 hours once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
|
Ixabepilone 40 mg/m^2 was administered as a 3-hour I.V. continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity. For the first cycle, ixabepilone was administered the day following the first dose of trastuzumab (in the first cycle trastuzumab was given on Day 0); in all the following cycles, ixabepilone was administered immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.
Other Names:
Trastuzumab was administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle at a dose of 2 mg/kg until disease progression or unacceptable toxicity.
In cycle 1, a loading dose of 4 mg/kg was administered as a 90-minute IV infusion on a day before initial administration of chemotherapy (i.e. on Day 0).
Trastuzumab was given immediately prior to ixabepilone (Arm A) or docetaxel (Arm B) in all subsequent cycles as a 30-minute IV infusion if the initial dose was well tolerated.
|
Active Comparator: Arm B
trastuzumab 4 mg/kg loading dose, then 2 mg/kg weekly + docetaxel 100 mg/m^2 IV over 1 hour once every 21 days (using a 21-day cycle); until disease progression or unacceptable toxicity.
|
Trastuzumab was administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle at a dose of 2 mg/kg until disease progression or unacceptable toxicity.
In cycle 1, a loading dose of 4 mg/kg was administered as a 90-minute IV infusion on a day before initial administration of chemotherapy (i.e. on Day 0).
Trastuzumab was given immediately prior to ixabepilone (Arm A) or docetaxel (Arm B) in all subsequent cycles as a 30-minute IV infusion if the initial dose was well tolerated.
Docetaxel 100 mg/m^2 was administered as a 1-hour IV continuous infusion on Day 1 in a 21-day cycle until disease progression or unacceptable toxicity.
For the first cycle, docetaxel was administered the day following the first dose of trastuzumab (i.e. in the first cycle trastuzumab was given on Day 0); in all following cycles, docetaxel was administered immediately after trastuzumab if the preceding dose of trastuzumab was well tolerated.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)
Time Frame: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)
|
Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 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 lesions.
CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment.
A two-sided confidence interval (CI) was computed using the Clopper-Pearson method.
|
Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)
|
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).
|
BOR was the best response recorded from the start of treatment until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30% reduction from baseline in the sum of the LD of all lesions.
CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment.
Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR.
Refer to Outcome Measure 3 for definition of PD.
|
Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).
|
Time in months from randomization until first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. PD=≥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. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method. |
From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).
|
Time to Response
Time Frame: From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)
|
Time to response was defined as the time in weeks from randomization until the measurement criteria are first met for a CR or PR, whichever is recorded first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method. |
From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)
|
Duration of Response
Time Frame: From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)
|
Period measured in months from time that measurement criteria were first met for CR or PR until first date of documented PD or death from any cause without prior documentation of progression. PD=≥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. Refer to Outcome Measure 1 for definitions of CR and PR. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by Brookmeyer and Crowley method. |
From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)
|
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 (maximum time that any participant was on therapy was 108 weeks.)
|
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 3=Severe; and Grade 4=Life-threatening or disabling.
GR=Grade.
|
Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
|
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Time Frame: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
|
Grade (GR)1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling.
Normal ranges provided by local laboratory and may also vary by age and sex.
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.
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.
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.
Hemoglobin:GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL;
GR3=<8.0-6.5g/dL,
GR4=<6.5g/dL.
LLN=lower limit of normal.
|
Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
|
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Time Frame: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
|
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.
Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=>ULN-2.5*ULN;
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.
ULN=upper limit of normal.
|
Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CA163-140
- Eudract No: 2007-000721-21
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Breast Cancer
-
Gilead SciencesRecruitingStudy of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors (ASCENT-J02)Advanced Solid Tumor | Metastatic Urothelial Cancer | Metastatic Triple-Negative Breast Cancer | HR+/HER2- Metastatic Breast CancerJapan
-
GlycoMimetics IncorporatedTerminatedBreast Cancer | Breast Cancer Metastatic | HR+ Metastatic Breast CancerUnited States
-
BriaCell Therapeutics CorporationRecruitingBreast Cancer | Breast Neoplasm | Metastatic Breast Cancer | Breast Cancer Metastatic | End Stage CancerUnited States
-
OBI Pharma, IncCompletedMetastatic Colorectal Cancer | Metastatic Lung Cancer | Metastatic Breast Cancer | Metastatic Gastric CancerTaiwan
-
Massachusetts General HospitalPuma Biotechnology, Inc.; Celcuity, Inc.WithdrawnMetastatic Breast Cancer | Invasive Breast Cancer | HER2-negative Breast Cancer | ER Positive Breast Cancer | PR-Positive Breast Cancer | Stage IV (Metastatic) Breast CancerUnited States
-
Novartis PharmaceuticalsCompletedMetastatic Breast Cancer | Postmenopausal Women | Locally Advanced Metastatic Breast CancerIsrael
-
Institut de Recherches Internationales ServierADIR, a Servier Group companyCompletedMetastatic Breast Cancer | Metastatic Triple Negative Breast CancerJapan, Belgium, France, Netherlands
-
Prof. Wolfgang JanniEli Lilly and CompanyRecruitingHormone Receptor-positive Metastatic Breast Cancer | HER2-negative Metastatic Breast CancerGermany, Switzerland
-
BriaCell Therapeutics CorporationLumaBridgeEnrolling by invitationBreast Cancer | Breast Neoplasm | Metastatic Breast Cancer | Breast Cancer MetastaticUnited States
-
Gustave Roussy, Cancer Campus, Grand ParisDaiichi SankyoRecruitingAdvanced Breast Cancer | HER2-positive Metastatic Breast Cancer | Breast Cancer Metastatic | HER2 Low Breast CarcinomaFrance
Clinical Trials on ixabepilone
-
Weill Medical College of Cornell UniversityBristol-Myers SquibbCompletedMetastatic Breast CancerUnited States
-
R-PharmNational Cancer Institute (NCI); Memorial Sloan Kettering Cancer CenterCompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
National Cancer Institute (NCI)CompletedLymphoma | Small Intestine Cancer | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Cedars-Sinai Medical CenterBristol-Myers SquibbTerminatedUrogenital Neoplasms | Adenocarcinoma | Carcinoma | Neoplasms, Glandular and Epithelial | Genital Neoplasms, Male | Prostatic Neoplasms | Prostatic Diseases | Genital Diseases, MaleUnited States
-
Eisai Inc.Completed
-
R-PharmCompletedSolid MalignanciesUnited States
-
R-PharmCompleted
-
R-PharmCompletedStomach NeoplasmsKorea, Republic of, Taiwan, Japan, Singapore, Hong Kong