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HER2-positive Breast CancerPhase 2NCT00077376

Trastuzumab, Ixabepilone, and Carboplatin in Treating Patients With HER2/Neu-Positive Metastatic Breast Cancer

A Phase 2 study testing trastuzumab, ixabepilone and carboplatin in people with HER2-positive Breast Cancer and Male Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying how well giving trastuzumab together with ixabepilone and carboplatin works in treating patients with HER2/neu-positive metastatic breast cancer. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
trastuzumab, ixabepilone and carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
1 siteUnited States
Study dates
Mar 2005to Mar 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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically confirmed adenocarcinoma of the breast which is metastatic and is known to overexpress HER2/neu who have received no prior chemotherapy for metastatic breast cancer; prior hormonal therapy for metastatic disease is allowed; NOTE: for this protocol, HER2 overexpression will be defined as 3+ HER2 positivity as measured by immunohistochemistry using the HercepTest (DAKO) or HER2 gene amplification as measured by fluorescent in-situ hybridization (FISH, e.g. Vysis); representative diagnostic tissue must be submitted for central diagnostic review
  • Patients must not be pregnant or breast feeding because of the teratogenic potential of these drugs; it is recommended that all females of childbearing potential have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective non-hormonal method of contraception
  • Patients must have at least one objective measurable disease parameter; baseline measurements and evaluations using RECIST criteria guidelines must be obtained within 4 weeks prior to registration to the study; NOTE: all areas of disease should be recorded and followed
  • Patients must have an ECOG performance status of 0 or 1
  • Patients must be disease free of prior malignancy for >= 5 years with the exception of curatively treated basal cell carcinoma or squamous cell carcinomas of the skin or carcinoma in situ of the cervix
  • Patients must not have a history of untreated brain metastasis or brain metastasis currently undergoing radiation; patients with brain metastasis representing the sole site of disease are not eligible for this study; patients with previously treated brain metastasis who have responded to brain radiotherapy and/or surgery and continue in response are eligible provided the brain is not the only site of measurable disease
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  • Patients must not have peripheral neuropathy of any grade
  • Patients must not have a history of prior severe (grade 3 or 4) hypersensitivity reaction to a drug formulated in polyoxyethylated castor oil (Cremophor EL)
  • Patients must have left ventricular ejection fraction by MUGA scan or echocardiogram that is at or above the lower institutional limits of normal obtained within 6 weeks prior to registration
  • Patients must not have a history of New York Heart Association class 3 or 4 heart failure
  • Serum creatinine =< 1.5 mg/dl
  • Granulocytes >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • SGOT(AST) and SGPT(ALT) =< 1.5 x upper limit of normal (unless liver is involved by tumor, in which case SGOT(AST) and SGPT(ALT) can be =< 2.0 x upper limit of normal)
  • Patients must have no history of prior therapy with trastuzumab (Herceptin), Ixabepilone (BMS-247550) or carboplatin for metastatic disease; patients who develop metastatic disease =< 6 months after completing adjuvant trastuzumab (Herceptin), paclitaxel, docetaxel, carboplatin, or Ixabepilone (BMS-247550) are considered to have had prior therapy for metastatic disease and are excluded from study participation
  • Patients must not have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2
  • Concurrent use of hormonal therapy is not permitted; concurrent radiation therapy is not permitted; hormonal therapy must have been discontinued >= 1 week prior to registration; radiation therapy must have been completed >= 2 weeks prior to registration
  • Patients may have had prior radiation therapy, but the previously irradiated tumors cannot be used to assess a clinical response; patients will not be eligible if they do not have other areas of measurable disease; an exception will be given for patients who have had tumor recurrence in an area that received adjuvant radiation treatments, such as the axilla or chest wall

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Trial of Trastuzumab Plus Weekly Ixabepilone(BMS-247550) and Carboplatin in Patients With HER2/Neu-Positive Metastatic Breast Cancer

This phase II trial is studying how well giving trastuzumab together with ixabepilone and carboplatin works in treating patients with HER2/neu-positive metastatic breast cancer. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as ixabepilone and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with ixabepilone and carboplatin may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the response rate (as determined by RECIST criteria) to combination therapy with Ixabepilone (BMS-247550), trastuzumab, and carboplatin in patients with metastatic breast cancer known to overexpress HER2.

SECONDARY OBJECTIVES:

  1. To determine time to disease progression (TTP) and time to treatment failure (TTF) after treatment with Ixabepilone (BMS-247550), trastuzumab and carboplatin in patients with metastatic breast cancer known to overexpress HER2.

II. To determine the toxicity of combination therapy with Ixabepilone (BMS-247550), trastuzumab and carboplatin in patients with metastatic breast cancer known to overexpress HER2.

III. To evaluate overall survival (OS) of combination therapy with Ixabepilone (BMS-247550), trastuzumab, and carboplatin in patients with metastatic breast cancer known to overexpress HER2.

IV. To correlate levels of phospho-STAT3 with levels of HER2, Survivin and EGFR expression as measured in tissue by immunohistochemistry.

OUTLINE: This is a multicenter study.

Induction therapy: Patients receive trastuzumab (Herceptin®) IV over 30 minutes* on days 1, 8, 15, and 22 and ixabepilone IV over 1 hour and carboplatin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.

NOTE: *Trastuzumab is given over 90 minutes on day 1 of course 1 (induction therapy) only.

Maintenance therapy: Patients receive trastuzumab IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years from study entry.

PROJECTED ACCRUAL: A total of 10-60 patients will be accrued for this study within 1-6 months.

Being tested
trastuzumab, ixabepilone, carboplatin, laboratory biomarker analysis
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, MOAB HER2

    Given IV

  • ixabepiloneDrug

    Also called BMS-247550, epothilone B lactam, Ixempra

    Given IV

  • carboplatinDrug

    Also called Carboplat, CBDCA, JM-8, Paraplat

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00077376
Study groupRoleWhat they receive
Treatment (trastuzumab, ixabepilone, carboplatin)ExperimentalInduction therapy: Patients receive trastuzumab (Herceptin®) IV over 30 minutes* on days 1, 8, 15, and 22 and ixabepilone IV over 1 hour and carboplatin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity. NOTE: *Trastuzumab is given over 90 minutes on day 1 of course 1 (induction therapy) only. Maintenance therapy: Patients receive trastuzumab IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: trastuzumab; Drug: ixabepilone; Drug: carboplatin; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study)

    To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up.

    The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.

    Measured: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

Secondary outcomes (7)

  1. Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study)

    To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up.

    The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks.

    Measured: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

  2. Time to Disease Progression for HER2+ Patients

    This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored.

    Measured: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

  3. Time to Disease Progression for All Treated Patients

    This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored.

    Measured: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

  4. Time to Treatment Failure for HER2+ Patients

    Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment.

    Measured: Assessed every cycle until treatment discontinuation

  5. Time to Treatment Failure for All Treated Patients

    Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment.

    Measured: Assessed every cycle until treatment discontinuation

  6. Kaplan-Meier Estimate of Overall Survival at 3 Years for HER2+ Patients

    Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years

  7. Kaplan-Meier Estimate of Overall Survival at 3 Years for All Treated Patients

    Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years.

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2004 (estimated)
  2. Study startMar 2005
  3. Primary completionMar 2009
  4. Study completionMar 2011

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00077376
Sponsor's protocol ID
NCI-2012-02946
Other IDs
NCI-2012-02946, U10CA023318, E2103, E2103, U10CA021115
Status last verified
Dec 2012
First submitted
10 Feb 2004
Last updated
21 May 2014

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing trastuzumab, ixabepilone and carboplatin in people with HER2-positive Breast Cancer and Male Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

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 18 inclusion and 0 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 21 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 4 Apr 2011). 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?

Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study) (time frame: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00077376.

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 21 May 2014.

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