Neo-Adjuvant Study in Triple Negative Breast Cancer Patients (ICE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
The Methodist Hospital System
ClinicalTrials.gov Identifier:
NCT01097642
First received: March 29, 2010
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

Ixabepilone and capecitabine combination has demonstrated to be an active regimen in patients with metastatic breast cancer (MBC) after failing an anthracycline and a taxane regimen. Cetuximab is active in tumors that express epidermal growth factor receptor (EGFR) with demonstrated activity in head and neck and colorectal tumors. A proportion of breast cancers are known to express EGFR. Cetuximab's mechanism of action suggests the possibility of efficacy in breast cancer patients, and several studies show that it may be efficacious in Triple Negative Breast Cancer (TNBC). This study seeks to evaluate Ixabepilone alone or in combination with cetuximab as a possible way to increase antitumor activity. In this randomized open-label phase II trial, patients will be randomized equally between 1) Ixabepilone or 2) Ixabepilone plus Cetuximab. Randomization will be stratified by disease stage (T1N1-3M0 or T2-4 N0-3M0).

The study's primary objective is to determine the pathologic complete response rate (pCR) (breast and axilla) of Ixabepilone versus Ixabepilone when combined with cetuximab in patients with invasive breast adenocarcinoma T1N1-N3M0 or T2-4 N0-3M0 disease who are triple negative and who are candidates for preoperative chemotherapy. The secondary objectives are to evaluate overall objective response rate in both treatment groups and to assess safety and toxicity of each regimen. There are also tertiary, exploratory objectives that will hopefully allow for the correlation of biomarker expression and response to treatment.


Condition Intervention Phase
Breast Cancer
Drug: Cetuximab
Drug: Ixabepilone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Open-Label Neo-Adjuvant Phase II Study Comparing Ixabepilone (I) Vs. Ixabepilone Plus Cetuximab (IC) in Triple Negative Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by The Methodist Hospital System:

Primary Outcome Measures:
  • Complete Response Rate [ Time Frame: one year after treatment ] [ Designated as safety issue: No ]
    The study's primary objective is to determine the pathologic complete response rate (pCR) (breast and axilla) of Ixabepilone versus Ixabepilone when combined with cetuximab in patients with invasive breast adenocarcinoma T1N1-N3M0 or T2-4 N0-3M0 disease who are triple negative and who are candidates for preoperative chemotherapy.


Secondary Outcome Measures:
  • Overall Objective Response Rate [ Time Frame: one year after treatment ] [ Designated as safety issue: No ]
    The secondary objectives are to evaluate overall objective response rate in both treatment groups.

  • Safety and toxicity of both treatment regimens [ Time Frame: one year after last treatment dose ] [ Designated as safety issue: Yes ]
    Baseline signs and symptoms will be recorded and followed throughout the trial. Toxicity assessments will be continuous during treatment and the year of follow-up, after which all study drug-related toxicities will be deemed resolved, stabilized, or irreversible. CTCAE v.3.0 will be used to grade toxicities. Vital signs will be performed at baseline and will be monitored pre-dose and during study drug administration for Cycles 1 - 4. Chemistry and hematology laboratory tests will be done at baseline and prior to each subsequent chemotherapy cycle.


Estimated Enrollment: 116
Study Start Date: October 2008
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ixabepilone Drug: Ixabepilone
Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
Other Name: azaepothilone B
Experimental: Ixabepilone plus Cetuximab Drug: Cetuximab
Cetuximab will be given at 400mg/m^2 IV over 120 minutes for its initial loading dose on day 1 of the first of four 21 day cycles. It will then be administered on a weekly basis at 250 mg/m^2 IV over 60 minutes.
Other Name: Erbitux
Drug: Ixabepilone
Ixabepilone will be given at 40mg/m^2 IV over 180 minutes on day 1 of each of four 21 day cycles.
Other Name: azaepothilone B

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologic confirmation of invasive breast carcinoma.
  • Patients must have intact primary tumor.
  • Patients greater than or equal to 18 years.
  • Patients should have T1N1-3M0 or T2-4 N0-3M0.
  • Patients with bilateral breast cancer are eligible.
  • Patients with second primary breast cancers are eligible.
  • Patients should have a Karnofsky performance scale of greater than or equal to 70%.
  • Patients must have clinically measurable disease to be treated in the neoadjuvant setting.
  • Patients should have adequate bone marrow function, as defined by peripheral granulocyte count of greater than or equal to 1500/mm^3, and platelet count greater than or equal to 100000mm^3.
  • Patients must have adequate liver function with a bilirubin within normal laboratory values. Alkaline phosphatase and transaminases (ALT and AST) may be up to 1.5 x upper limit of normal (ULN) of the institution.
  • Patients should have adequate renal function with creatinine levels within normal range.
  • Patients should have a normal left ventricular ejection fraction (LVEF) of greater than or equal to 50%.
  • Negative serum or urine pregnancy test for a woman of childbearing potential (WOCBP).
  • WOCBP must use a reliable and appropriate contraceptive method during the study and six months after chemotherapy is completed. WOCBP are women who are not menopausal for 12 months or had no previous surgical sterilization.
  • Patients must agree to have study biopsies.
  • Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.

Exclusion Criteria:

  • Patients with a history of other invasive malignancies diagnosed and treated within the previous 5 years, except non-melanoma skin cancer and non-invasive cervical cancer.
  • Her2Neu, ER and PR positive patients should be excluded.
  • Patients with Inflammatory breast cancer (IBC) are excluded.
  • Patients with an organ allograft or other history of immune compromise.
  • Prior treatment with any investigational drug within the preceding 4 weeks.
  • Chronic treatment with systemic steroids or another immunosuppressive agent.
  • A Known history of HIV seropositivity.
  • Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin defined as 1 mg a day).
  • Other concurrent and/or uncontrolled medical disease which could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, unstable angina, or congestive heart failure - New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months, chronic liver or renal disease, active upper GI tract ulceration).
  • Patients with a pre-existing peripheral neuropathy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01097642

Locations
United States, Texas
The Methodist Hospital Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
The Methodist Hospital System
Bristol-Myers Squibb
Investigators
Principal Investigator: Jenny Chang, MD The Methodist Hospital Research Institute
  More Information

No publications provided

Responsible Party: The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT01097642     History of Changes
Other Study ID Numbers: 0908-0265
Study First Received: March 29, 2010
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Epothilones
Cetuximab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 14, 2014