Triple Negative Locally Advanced Non-resectable Breast CancerPhase 2NCT00633464
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
A Phase 2 study testing ixabepilone and ixabepilone + cetuximab in people with Triple Negative Locally Advanced Non-resectable Breast Cancer and Metastatic Breast Cancer, run by R-Pharm at 19 sites in 7 countries.
Trial summary
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)… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple Negative Locally Advanced Non-resectable Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- ixabepilone and ixabepilone + cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 19 sitesin 7 countries
- Study dates
- Jun 2008to May 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Tumors that are fluorescence in situ hybridization test (FISH) positive or immunohistochemistry (IHC) 3+
- Neuropathy > Grade 1
- Prior systemic therapy for metastatic disease
Trial locations and contacts
19 sites in 7 countries.
19 sites in 7 countries
France7 sites
Local Institution
Bayonne, 64100
Local Institution
Dijon, 21079
Local Institution
Lyon, 69008
Local Institution
Paris, 75651
Local Institution
Saint-Brieuc, 22015
Local Institution
Saint-Herblain, 44805
Local Institution
Toulouse, 31052
Czechia3 sites
Local Institution
Brno, 656 53
Local Institution
Prague, 128 08
Local Institution
Prague, 150 06
Spain3 sites
Local Institution
Barcelona, 08036
Local Institution
Barcelona, 08208
Local Institution
Barcelona, 08221
About this study
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
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
- Being tested
- ixabepilone, ixabepilone + cetuximab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ixabepiloneDrug
Also called IXEMPRA, BMS-247550
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.
ixabepilone + cetuximabDrug
Also called IXEMPRA, BMS-247550, ERBITUX, BMS-564717
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (ixabepilone 40 mg^2) | Experimental | ixabepilone 40 mg/m^2 every 3 weeks Receives: Drug: ixabepilone |
| Arm B (cetuximab 250 mg/m^2 + ixabepilone 40 mg/m^2) | Experimental | cetuximab 400 mg/m^2 loading dose then 250 mg/m^2 weekly + ixabepilone 40 mg/m^2 every 3 weeks Receives: Drug: ixabepilone + cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Objective Response (OR; Using Response Evaluation Criteria in Solid Tumors [RECIST])
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.
Measured: 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)
Number of Participants With Best Overall Response as Assessed With Response Criteria in Solid Tumors (RECIST)
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.
Measured: 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).
Secondary outcomes (6)
Progression Free Survival (PFS)
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.
Measured: From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 17 months)
Time to Response
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.
Measured: 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.)
Duration of Response
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.
Measured: 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)
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
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.
Measured: 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)
Number of Participants With Hematology Abnormalities
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.
Measured: 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)
Number of Participants With Serum Chemistry Abnormalities
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2008 (estimated)
- Study startJun 2008
- Primary completionSep 2010
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Triple Negative Locally Advanced Non-resectable Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- R-Pharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00633464
- Sponsor's protocol ID
- CA163-139
- Status last verified
- Feb 2016
- First submitted
- 5 Mar 2008
- Last updated
- 10 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00633464
- Acronym / sponsor ID
- CA163-139
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- R-PharmIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 12 Mar 2008 (estimated)
- Results
- Posted 24 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (ixabepilone 40 mg^2) | Experimental | Drug: ixabepiloneixabepilone 40 mg/m^2 every 3 weeks |
| Arm B (cetuximab 250 mg/m^2 + ixabepilone 40 mg/m^2) | Experimental | Drug: ixabepilone + cetuximabcetuximab 400 mg/m^2 loading dose then 250 mg/m^2 weekly + ixabepilone 40 mg/m^2 every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (3 listed)
- Tumors that are fluorescence in situ hybridization test (FISH) positive or immunohistochemistry (IHC) 3+
- Neuropathy > Grade 1
- Prior systemic therapy for metastatic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ixabepiloneAlso: IXEMPRA, BMS-247550injection, 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. | Drug | Arm A (ixabepilone 40 mg^2) |
| ixabepilone + cetuximabAlso: IXEMPRA, BMS-247550, ERBITUX, BMS-564717Ixabepilone: 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. | Drug | Arm B (cetuximab 250 mg/m^2 + ixabepilone 40 mg/m^2) |
Primary outcome
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)
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).
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.
6 secondary outcomes
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)
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.)
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)
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
19 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ixabepilone and ixabepilone + cetuximab in people with Triple Negative Locally Advanced Non-resectable Breast Cancer and Metastatic Breast Cancer, run by R-Pharm at 19 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in France, Czechia, Spain, Austria, Poland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2016.