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HER2-positive Breast CancerPhase 2NCT00079326

Trastuzumab and Ixabepilone in Treating Women With HER2-Positive Metastatic Breast Cancer

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

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial is studying how well giving trastuzumab together with ixabepilone works in treating women with HER2-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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
trastuzumab, ixabepilone and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
Jan 2004to Oct 2010
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

  • Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease
  • Tumors must be HER2 overexpressing; acceptable methods of measurement of HER2 expression include immunohistochemistry IHC) and fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive for HER2 overexpression; tumors tested by FISH must be positive by the specific FISH assay for genetic amplification of HER2; tumors that are 3+ by IHC, but negative by FISH assay are ineligible; consideration should be given to performing a repeat biopsy, with reanalysis for HER2 overexpression, in patients who have received prior trastuzumab, as little data exist on the persistence of HER2 overexpression after prior treatment with trastuzumab; biopsy in this circumstance, however, is not required
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan; the protocol will employ the RECIST criteria
  • Prior Therapy - Two cohorts of patients will be treated on this treatment regimen; the two cohorts are determined by prior therapy and are as follows:
  • Treatment Cohort 1:
  • Chemotherapy: metastatic breast cancer: Patients in treatment Cohort 1 may NOT have received prior chemotherapy or prior trastuzumab therapy for metastatic breast cancer; patients may have received prior hormonal therapy for metastatic breast cancer
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  • Chemotherapy: early stage breast cancer: Patients in treatment Cohort 1 may have received prior chemotherapy and/or hormonal therapy for early stage breast cancer; patients must be at least 6 months from prior chemotherapy received in the adjuvant setting
  • Trastuzumab: Patients in treatment Cohort 1 may have received trastuzumab in the adjuvant setting, provided that trastuzumab therapy ended at least 12 months prior to study participation; patients may not have previously received trastuzumab in the metastatic setting
  • Radiation therapy: Patients in treatment Cohort 1 may have received prior radiation therapy in either the metastatic or early stage settings; radiation therapy must be completed at least 7 days prior to study participation
  • Hormonal therapy: Patients in treatment Cohort 1 may have received hormonal therapy (therapies) in the adjuvant or metastatic setting; patients must discontinue hormonal therapy 2 weeks prior to study participation; patients with overt disease progression on prior hormonal therapy are eligible without waiting two weeks after discontinuing hormonal therapy, but must discontinue hormonal treatments prior to study participation
  • Treatment Cohort 2:
  • Chemotherapy: metastatic breast cancer: Patients in treatment Cohort 2 may have received up to two prior chemotherapy regimens for metastatic breast cancer; prior trastuzumab or other biologic or immunologic therapies are not considered to be chemotherapeutic regimens unless they were administered in conjunction with a chemotherapeutic agent; patients may have received prior hormonal therapy for metastatic breast cancer
  • Chemotherapy: early stage breast cancer: Patients in treatment Cohort 2 may have received prior chemotherapy and/or hormonal therapy for early stage breast cancer; if adjuvant chemotherapy was completed less than 6 months prior to the diagnosis of metastatic disease, the adjuvant regimen will be considered one of the two possible metastatic regimens
  • Trastuzumab: Patients in treatment Cohort 2 must have received one prior trastuzumab-containing regimen either in the metastatic setting or in the adjuvant setting; if the trastuzumab was administered in the adjuvant setting, disease recurrence must have occurred within 12 months of completion of adjuvant therapy
  • Radiation therapy: Patients in treatment Cohort 2 may have received prior radiation therapy in either the metastatic or early stage settings; radiation therapy must be completed at least 7 days prior to study participation
  • Hormonal therapy: Patients in treatment Cohort 2 may have received hormonal therapy (therapies) in the adjuvant or metastatic setting; patients must discontinue hormonal therapy 2 weeks prior to study participation; patients with overt disease progression on prior hormonal therapy are eligible without waiting two weeks after discontinuing hormonal therapy, but must discontinue hormonal treatments prior to study participation
  • Life expectancy of greater than 6 months
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Patients must have adequate organ and marrow function as defined below; laboratory tests should be completed within 14 days prior to registration; left ventricular ejection fraction (LVEF) may be determined by either echocardiography or nuclear scintigraphy (i.e. MUGA scan or RVG), and should be obtained within 28 days prior to registration
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • ALT(SGPT) =< 5 X institutional upper limit of normal
  • LVEF >= 50%
  • Concurrent Therapy: patients may not receive concurrent hormonal therapy, chemotherapy, or radiation treatments while on study; patients requiring radiation therapy during protocol-based treatment will be taken off study; if patients develop intraparenchymal brain metastases while on treatment, but do not have evidence of other systemic progression, they will be allowed to resume treatment with the combination once their radiation has been completed; they will be allowed to continue trastuzumab therapy during radiation, at the treating physician's discretion; nevertheless, the date of discovery of the CNS disease will still be considered the date of disease progression; patients may receive concurrent bisphosphonate therapy (e.g. pamidronate) while on study; patients may not receive other experimental treatments while on study
  • The effects of BMS-247550 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patient Registration and Data Submission: Patients will be registered by contacting and faxing the completed eligibility checklist and all pages of the consent form to the Quality Assurance Office of Clinical Trials (QACT) at the Dana-Farber Cancer Institute; please fax to 617-632-2295 or telephone at 617-632-3761; a research nurse, Kathryn Clarke, will be available at 617-632-3478 to answer any protocol-related questions; you many also contact the study coordinator, Keri Hannagan, at 617-632-5584
  • Regular data submissions should be made to Dana-Farber Cancer Institute's QACT; please fax all data in a timely manner to the number above

Who cannot join

  • Patients may not be receiving any other investigational antitumor agents
  • Patients with leptomeningeal carcinomatosis are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with a history of brain metastases are eligible, providing that they have completed treatment for their brain metastases at least 1 week prior to enrollment, are asymptomatic from their brain metastases and are not taking steroids; screening for CNS disease is not required if patients do not have symptoms that might be related to CNS metastases; patients with such symptoms should be evaluated for the possibility of CNS disease prior to study participation
  • Patients with a history of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study are ineligible; patients with a history of severe Cremophor reactions should be excluded; patients who experienced grade 1 or 2 hypersensitivity reactions to prior trastuzumab or taxane therapies are eligible IF these reactions did not prevent previous administration of such agents; patients who were deemed inappropriate candidates for trastuzumab or taxane-based treatments based on their hypersensitivity reactions are not eligible
  • Received prior epothilone therapy
  • Grade 2 or greater neuropathy (neuromotor or neurosensory)
  • Received prior high dose chemotherapy with bone marrow transplant or peripheral blood stem cell support within 2 years of study entry
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because BMS-247550 and trastuzumab are agents which may have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued if the mother is treated on study
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with agents administered during the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 2 Study of Trastuzumab in Combination With BMS-247550 in Women With Metastatic Breast Cancer

This phase II trial is studying how well giving trastuzumab together with ixabepilone works in treating women with HER2-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, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with ixabepilone may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Examine the response rate of HER2-positive metastatic breast cancer to combination therapy with trastuzumab and BMS-247550 in two cohorts of women: a. women who have received no prior chemotherapy or trastuzumab for their metastatic breast cancer; b. women who have received prior trastuzumab therapy (either for metastatic disease or prior adjuvant trastuzumab if < 1 year since completion of adjuvant trastuzumab therapy) and up to 2 prior chemotherapeutic regimens in the metastatic setting.

SECONDARY OBJECTIVES:

  1. To characterize the safety and toxicity profile of trastuzumab in combination with BMS-247550.

II. To determine the time-to-disease-progression (TTP) and time-to-treatment-failure (TTF) for patients receiving trastuzumab in combination with BMS-247550 in each cohort.

III. Analyze various tissue biomarkers (e.g. HER2/phospho-HER2, EGFR/phospho-EGFR, IGRF-I, phospho-MAPK, phospho-P13K, bcl-2, bcl-xL, MDR-1, MRP and β-tubulin) and blood biomarkers (HER2-extracellular domain [ECD], circulating tumor cells) to correlate them with response to treatment.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to prior trastuzumab (Herceptin®) therapy (with or without chemotherapy) for metastatic breast cancer (yes vs no).

Patients receive trastuzumab IV over 30-90 minutes and ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Being tested
trastuzumab, ixabepilone, laboratory biomarker analysis
Medical subject headings
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

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00079326
Study groupRoleWhat they receive
Treatment (trastuzumab, ixabepilone)ExperimentalPatients receive trastuzumab IV over 30-90 minutes and ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: trastuzumab; Drug: ixabepilone; Other: laboratory biomarker analysis

What is being measured

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

  1. Overall Response Rate

    Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by computed tomography or magnetic resonance imaging scans: Complete response (CR) is defined as the disappearance of all target lesions; Partial Response is defined by at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response Rate (ORR) = CR + PR.

    Measured: Up to 6 years

Secondary outcomes (1)

  1. Time to Treatment Failure (TTF)

    Time to Treatment Failure as determined by RECIST v.1.0 Criteria: is the time from the date of randomization or start of treatment to the earliest date of progression, date of death due to any cause, or date of discontinuation due to reasons of adverse events, abnormal laboratory values, abnormal test procedure results, subject withdraws consent, or date 'Lost to follow up'.

    Measured: up to 6 years

Timeline

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

  1. First posted10 Mar 2004 (estimated)
  2. Study startJan 2004
  3. Primary completionJul 2008
  4. Study completionOct 2010

Why it stopped: Slow accrual.

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00079326
Sponsor's protocol ID
NCI-2012-03123
Other IDs
NCI-2012-03123, CDR0000355176, 03-202, 6297, P30CA006516, N01CM62206
Status last verified
Jan 2013
First submitted
8 Mar 2004
Last updated
2 Jun 2014

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing trastuzumab, ixabepilone and laboratory biomarker analysis in people with HER2-positive Breast Cancer and Recurrent 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 29 inclusion and 9 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: stopped early, as of the sponsor's last update on 2 Jun 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 6 Feb 2014). 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?

Overall Response Rate (time frame: Up to 6 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 NCT00079326.

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 2 Jun 2014.

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