E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Female Subjects with Her2+ Locally Advanced and/or Metastatic Breast Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057654 |
E.1.2 | Term | Breast cancer female |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the response rate for ixabepilone plus trastuzumab and the response rate for docetaxel plus trastuzumab in female subjects with Her2+ locally advanced and/or metastatic breast cancer not previously treated with chemotherapy or trastuzumab in the metastatic setting. |
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E.2.2 | Secondary objectives of the trial |
To estimate the progression free survival for both treatment arms. To estimate time to response for both treatment arms. To estimate the duration of response for both treatment arms. To determine the safety and tolerability of ixabepilone/trastuzumab and docetaxel/trastuzumab in this subject population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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. 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. Patients 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 patients enrolled would be such that no clinically significant information would be collected. |
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E.4 | Principal exclusion criteria |
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 >= 1.5 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the Objective Response (OR). A subject will have an OR if their best overall response during the study is either a Complete Response (CR) or a Partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |