Trial of Ixabepilone in Patients With HER-2 Negative Metastatic Breast Cancer (HIT)

This study has been terminated.
(The low accrual rate of the study (25% of the expected accrual rate))
Sponsor:
Information provided by:
Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00790894
First received: November 13, 2008
Last updated: May 17, 2011
Last verified: May 2011
  Purpose

This is a Phase II Randomized, Open Label, Non-comparative Trial (Parallel Assignment and Efficacy Study) for patients with HER-2 Negative Metastatic Breast Cancer Previously Treated With chemotherapy in the Neo-Adjuvant or Adjuvant Setting.Patients will be randomized to receive Ixabepilone either every three weeks, or weekly for three weeks followed by one week off. Patients will be treated until consent withdrawal, intolerable toxicity or documented disease progression


Condition Intervention Phase
Metastatic Breast Cancer
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: Phase II Randomized Trial of Ixabepilone Administered Weekly or Every Three Weeks in Patients With HER-2 Negative Metastatic Breast Cancer Previously Treated With Chemotherapy in the Neo-adjuvant or Adjuvant Setting

Resource links provided by NLM:


Further study details as provided by Hellenic Cooperative Oncology Group:

Primary Outcome Measures:
  • The primary endpoint of the study is the best Overall Response (OR). [ Time Frame: At 6, 12 and 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy endpoints: time to response, PFS, TTF, duration of response [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • OS Toxicity endpoints: incidence of hematological and non-hematological toxicities [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • Translational endpoints [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]

Enrollment: 64
Study Start Date: November 2008
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: ixabepilone
Arm A: ixabepilone will be given at a dose of 40 mg/m2 as a 3-hour intravenous infusion on Day 1 in a 21 days cycle.
Experimental: 2 Drug: ixabepilone
Arm B: ixabepilone will be given at a dose of 20 mg/m2 as a 3-hour intravenous infusion on Days 1, 8 and 15, then 1 week off in a 28-days cycle.

Detailed Description:

Patients with measurable metastatic breast cancer that have been treated in the adjuvant or neo-adjuvant setting with chemotherapy will be considered for this study. Subjects must not have received cytotoxic chemotherapy for locally recurrent/metastatic disease. Patients who fulfil the eligibility criteria, and have signed inform consent for the trial will be centrally randomized by electronic means to one of two ixabepilone treatment arms. Stratification factors will include: time to recurrence from adjuvant treatment, calculated from the date of the last dose of adjuvant treatment to the date of relapse (≤ 1 year vs. > 1 year); and previous chemotherapy with taxane regimen in the neo-adjuvant or adjuvant setting (yes vs. no). Randomization will be balanced by site.Treatment Protocol· Arm A [standard once every three weeks schedule]:Ixabepilone [BMS-247550] will be administered on Day 1 (D1) every three weeks as a 3-hour infusion at a dose of 40 mg/m2. · Arm B [weekly schedule]:Ixabepilone [BMS-247550] will be administered weekly for three weeks as a 3-hour infusion at a dose of 20 mg/m2, followed by one week-off.Treatment can be continued until consent withdrawal by the patient, intolerable toxicity or documented disease progression.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Female patients aged 18 to 75 years inclusive
  • Prior chemotherapy in the adjuvant or neo-adjuvant setting
  • Diagnosis of HER-2 negative (HER-2 <2+ by immunohistochemistry and/or FISH negative) metastatic breast adenocarcinoma confirmed by the pathology department of the enrolling institution
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Life expectancy of at least 12 weeks
  • Measurable disease by the Response Criteria in Solid Tumors (RECIST) method
  • Laboratory values within the specified ranges within 1 week of study enrolment:
  • Absolute neutrophil count of ≥ 1.5 x 109/L
  • Thrombocyte count of ≥ 100 x 109/L
  • Subjects must not have received cytotoxic chemotherapy for locally recurrent/metastatic disease
  • Prior hormonal therapy for locally recurrent or metastatic disease allowed
  • AST and ALT ≤ 2.5 x ULN
  • Bilirubin ≤ 1.5 x ULN
  • Recovery from prior palliative radiotherapy for bone metastases

Exclusion Criteria:

  • Because of concerns that ixabepilone metabolism may be inhibited by potent cytochrome P450 3A4 inhibitors, patients must not receive the following medications, up to 72 hours prior to initiation of study therapy and until they come off treatment with ixabepilone: amprenavir, delavirdine, voriconazole, erythromycin, cyclosporine, troleandomycin, terfenadine, ketoconazole, nelfinavir, and ritonavir
  • Patients with CTC grade 2 or greater neuropathy at baseline
  • Patients with any history or evidence of brain an/or leptomenigneal metastasis
  • Patients with clinically significant cardiac disease (e.g. unstable angina, congestive heart failure, myocardial infarction) within 6 months from study entry
  • Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocol
  • Any concurrent active malignancy other than non-melanoma skin cancer or in situ carcinoma of the cervix (subjects with a history of previous malignancies but without evidence of disease for 5 years will be allowed to enter the trial)
  • Prior severe HSR to agents containing Cremophor EL
  • Women of childbearing potential (WOCBP) who are unwilling or unable to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks from the last dose of ixabepilone, in such a manner that the risk of pregnancy is minimized WOCBP include: any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; women on hormone replacement therapy with documented FSH level > 35mIU/mL. Even women who are practising abstinence or whom their partner is sterile (e.g. vasectomy) should be considered of childbearing potential.
  • Women who are pregnant or breastfeeding
  • Women with a positive pregnancy test on enrolment or prior to study therapy
  • No other concomitant chemotherapy, endocrine therapy, immunotherapy, radiation therapy (except for palliative radiotherapy for bone metastases) or investigational treatments are allowed during subject's participation in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790894

Locations
Greece
University Hospital Attikon, Second Department of Internal Medicine, Oncology Section
Athens, Greece, 12462
Alexandra Hospital, Department of Clinical Therapeutics
Athens, Greece
Agii Anargiri Cancer Hospital, Third Department of Medical Oncology
Athens, Greece, 13122
Hippokration General Hospital, Oncology Department
Athens, Greece, 11527
Hygeia Hospital, First Deparment of Medical Oncology
Athens, Greece, 15123
Hygeia Hospital, Second Department of Medical Oncology
Athens, Greece, 15123
University General Hospital of Ioannina, Medical Oncology Department
Ioannina, Greece, 45500
University Hospital of Larisa, Department of Medical Oncology
Larisa, Greece, 41110
University Hospital of Patras, Department of Medicine, Division of Oncology
Patras, Greece, 265 00
Metropolitan Hospital, First Department of Medical Oncology
Piraeus, Greece, 18547
Metropolitan Hospital, Second Dept of Medical Oncology
Piraeus, Greece, 18547
"Papageorgiou" General Hospital, Department of Medical Oncology
Thessaloniki, Greece, 56429
"Theageneio" Cancer Hospital, Third Department of Medical Oncology
Thessaloniki, Greece, 54007
Sponsors and Collaborators
Hellenic Cooperative Oncology Group
Investigators
Principal Investigator: George Fountzilas Papageorgiou General Hospital
  More Information

No publications provided by Hellenic Cooperative Oncology Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: G. Fountzilas/President, Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00790894     History of Changes
Other Study ID Numbers: HE 11A08
Study First Received: November 13, 2008
Last Updated: May 17, 2011
Health Authority: Greece: National Organization of Medicines

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

ClinicalTrials.gov processed this record on August 28, 2014