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

NCT00079326 | Terminated Phase 2 Results

• 6 other identifiers: NCI-2012-03123CDR000035517603-2026297P30CA006516N01CM62206
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (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.

  Up to 6 years

Secondary Outcomes (1)

• Time to Treatment Failure (TTF)

  up to 6 years

Study Arms (1)

Treatment (trastuzumab, ixabepilone)

EXPERIMENTAL

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.

Biological: trastuzumab; Drug: ixabepilone; Other: laboratory biomarker analysis

Interventions

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

Treatment (trastuzumab, ixabepilone)

ixabepilone DRUG

Given IV

Also known as: BMS-247550, epothilone B lactam, Ixempra

Treatment (trastuzumab, ixabepilone)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (trastuzumab, ixabepilone)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; ixabepilone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Craig Bunnell
• Organization: Dana-Farber Cancer Institute

cbunnell@partners.org

617-632-3800

Study Officials

• Craig Bunnell

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 10, 2004
• Study Start: January 1, 2004
• Primary Completion: July 1, 2008
• Study Completion: October 1, 2010
• Last Updated: June 2, 2014
• Results First Posted: February 6, 2014

Record last verified: 2013-01

Locations

US (1)