Randomized Phase II study of Ixabepilone Plus Trastuzumab vs. Docetaxel Plus Trastuzumab in Female Subjects with Her2+ Locally Advanced and/or Metastatic Breast Cancer+ Revised Protocol 01, incorporating Amendment 01 (v1.0, dated 01-Oct-2007)
- Conditions
- Female Subjects with Her2+ Locally Advanced and/or Metastatic Breast CancerMedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer
- Registration Number
- EUCTR2007-000721-21-GR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 80
1. Signed Written Informed Consent
2. Target Population
a) Histologic or cytologic confirmed diagnosis of invasive adenocarcinoma originating in the breast with evidence of locally advanced and/or metastatic disease.
b) At least one target lesion per RECIST criteria. Locally advanced disease must not be amenable to resection with curative intent. Previously radiated area(s) must not be the only measurable site of disease.
c) Subjects must not have received cytotoxic chemotherapy for locally advanced and/or metastatic disease.
d) Subjects may have received neo adjuvant chemotherapy, but subjects relapsing within 12 months after their last dose of an (neo)adjuvant taxane are not allowed into the study.
e) Subjects must not have received prior trastuzumab therapy for locally advanced and/or metastatic disease. Subjects who have received prior (neo)adjuvant trastuzumab are eligible for this study except for subjects who relapsed within 12 months after the last dose of trastuzumab given as (neo)adjuvant therapy.
f) Subjects must have breast cancer known to over express or amplify Her2 (i.e., 3+ by immunohistochemistry and/or FISH positive).
g) Prior endocrine therapy in (neo)adjuvant, recurrent or metastatic setting is allowed, but this must have been discontinued at least 2 weeks prior to randomization. Subjects who have received hormonal therapy for metastatic breast cancer must have documented progression.
h) Karnofsky Performance Status (PS) of 80-100 (or ECOG, PS of 0-1) (See Protocol Appendix 2).
i) Estimated life expectancy of at least 12 weeks.
j) Recovery from toxicity (except for alopecia, myalgia, fatigue, Grade 1 neuropathy) of recent therapy, including chemotherapy, immunotherapy, biological therapy or investigational product. Any such therapy must have been completed at least 3 weeks prior to randomization.
k) Recovery from recent toxicity from surgery; at least one week must have elapsed from minor surgery (e.g. placement of venous access device or fine needle aspiration), at least 4 weeks from major surgery.
l) Recovery from radiation; at least one week from focal/palliative radiation therapy and 3 weeks from any therapeutic radiation.
m) Left Ventricular Ejection Fraction (LVEF) >= 50%.
n) Accessible for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating center.
3. Women 18 years of age or older.
Male subjects will be excluded from this trial. Due to the small size population of this trial the expected number of male subjects enrolled would be such that no clinically significant information would be collected.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 12 weeks after the last dose of docetaxel or ixabepilone, and for at least 24 weeks after the last dose of trastuzumab.
b) Women who are pregnant or breastfeeding.
c) Women with a positive pregnancy test on enrollment or prior to study therapy.
2. Target Disease Exceptions
a) Evidence of baseline sensory or motor neuropathy > Grade 1.
b) Any current or previous history of brain and/or leptomeningeal metastases
including evidence of cerebral edema by computerized tomography (CT) or magnetic resonance imaging (MRI)
c) Prior radiation must not have included >= 30% of major bone marrow containing areas (pelvis, lumbar spine).
3. Medical History and Concurrent Diseases
a) Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled or the control of which may be jeopardized by this therapy.
b) Any concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ 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.
c) Clinically significant cardiovascular disease (e.g. unstable angina, congestive heart failure, myocardial infarction) within 6 months prior to study entry.
d) Prior history of high dose chemotherapy with bone marrow transplant or peripheral blood stem cell transplant within the last 2 years.
e) Prior treatment with an epothilone (or epothilone analogue).
4. Physical and Laboratory Test Findings
a) Absolute neutrophil count (ANC) =< 1500/mm³,
b) Hemoglobin =< 9 g/dL,
c) Platelets < 100,000/mm³,
d) Total bilirubin > 1.5x times the upper limit of normal (ULN),
e) AST or ALT >= 2.5 x ULN.
5. Allergies and Adverse Drug Reactions
a) Known allergy to any of the study drugs or their excipients such as, prior severe HSR to agents containing Cremophor®EL; or allergies to Chinese hamster ovary cell proteins or other recombinant humanized antibodies.
i. Prior Grade 1 or 2 hypersensitivity reaction to taxane therapies
allowed provided drug administration was possible.
6. Prohibited Treatments and/or Therapies
a) Subjects must not continue or institute treatment with the following strong inhibitors of CYP3A4 within 72 hours prior to the initiation of study therapy until end of treatment with ixabepilone or docetaxel: amiodarone, clarithromycin, amprenavir, delavirdine, voriconazole, erythromycin, fluconazole, itraconazole, ketoconazole, indinavir, nelfinavir, ritonavir, and saquinavir.
b) Other concurrent anti-tumor chemotherapy, hormonal therapy, immunotherapy regimens or radiation therapy, standard or investigational.
7. Prisoners or subjects who are compulsorily detained
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method