| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Breast cancer, first line |
|
| 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 | 10006187 |
| E.1.2 | Term | Breast cancer |
|
| 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 of ixabepilone monotherapy, and the combination of ixabepilone plus cetuximab as first-line treatment of female subjects with triple negative (ER, PR, Her2 negative) locally advanced non-resectable and/or metastatic breast cancer. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives are to estimate the progression-free survival, time to response and duration of response in both arms and to determine the safety and tolerability of ixabepilone monotherapy and ixabepilone/cetuximab in this subject population. |
|
| 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 non-resectable and/or metastatic disease. b) At least one target lesion per RECIST criteria. c) Previously radiated area(s) must not be the only site of disease. d) Subjects must have breast cancer not overexpressing or amplify Her2: IHC 0 and 1+ tumors are allowed into the study unless FISH is positive. IHC 2+ tumors are allowed into the study only if FISH is negative. Her2 status will be determined based on local measurements that have been done at diagnosis (based on the primary tumor), or based on re-biopsy. Measurements of the primary tumor will not be considered if a valid measurement of the metastasis is available. e) Subjects must have breast cancer that does not express any hormone receptors (ER and/or PR). Hormone receptor status will be determined based on local measurements that have been done at diagnosis (based on the primary tumor), or based on re-biopsy. Measurements of the primary tumor will not be considered if a valid measurement of the metastasis is available. f) Subjects must have had prior adjuvant or neoadjuvant anthracycline-based chemotherapy 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. h) Karnofsky Performance Status (PS) of 80-100 (or Eastern Cooperative Oncology Group, PS of 0-1) (See Protocol Appendix 3). i) Estimated life expectancy of at least 12 weeks. j) Recovery (except for alopecia, fatigue and grade 1 neuropathy) from 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 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) Accessible for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating center 3) Age and Sex a) 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. |
|
| 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 and for up to 12 weeks after the last dose of any study drug. b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration. 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. c) Prior radiation must not have included ≥ 30% of major bone marrow containing areas (pelvis, lumbar spine). d) Subjects who have received prior systemic therapy for metastatic disease. e) Tumors excluded from the study are the ones that are FISH positive or IHC 3+. 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 previous 2 years. e) Prior treatment with an epothilone (or epothilone analogue) or an EGFR inhibitor. 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 > 1.0x 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 Hypersensitivity Reaction (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 strong inhibitors of CYP3A4 from 72 hours prior to the initiation of study therapy until end of treatment with ixabepilone (e.g., ketoconazole, itraconazole, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, or voriconazole). b) Other concurrent anti-tumor chemotherapy, hormonal therapy, immunotherapy regimens or radiation therapy, standard or investigational. 7) Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. |
|
| 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 Tumours (RECIST) criteria. Tumor response will be assessed for all randomized subjects and will be evaluated using the RECIST criteria. Tumor assessments will be performed every 6 weeks for the first 12 months and every three months after that until disease progression. Safety information will be collected for all subjects enrolled in the study. Laboratory values, adverse events and other symptoms will be graded according to the NCI CTC Version 3.0 |
|
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Ixabepilone in monoter. vs Ixabep. + Cetuximab |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
|
| La sperimentazione sara' completata quando tutti i soggetti avranno mostrato segni di miglioramento o 15 mesi dopo l'ultima visita all'ultimo paziente (LPLV). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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