E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10006187 |
E.1.2 | Term | Breast cancer |
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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 investigate whether the addition of bortezomib to a SERM or AI will show clinical activity in patients with documented progressive disease while being treated with the identical endocrine agent. Clinical activity is defined by clinical benefit which consists of these patients obtaining at least either stable disease, partial or complete response according to RECIST criteria, for at least 8 weeks, since the start of Velcade (41). This should occur in at least 2 patients in the first 14 evaluable patients from both either treatment group A or B (see below) which equals to a clinical benefit of > 7%. |
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E.2.2 | Secondary objectives of the trial |
to define the activity of the NF-kappa B initiated pathway in tumors of patients whose disease progresses and thus experiencing clinically defined (RECIST) endocrine resistance, - to elucidate the changes in the ER and NF-kappaB pathway in the patients after treatment with bortezomib, if possible in tumor tissue.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Female adult (> 18 years) patients with metastatic breast cancer, 2) Postmenopausal status defined as either a. > 55 years b. bilateral ovariectomy c. < 55 years with menopausal FSH levels d. patients on LH-RH agonists in combination with either SERM or AI must continue the LHRH agonist, 3) ER and/or PgR + disease (at least 10% of nuclei in the initial are either ER or PgR positive) as defined in the participating institution, 4) Measurable disease by RECIST, 5) All patients should have been treated either in the adjuvant or metastatic setting with tamoxifen and an AI, 6) Radiologically documented disease progression of disease as defined by RECIST criteria after second line (if prior adjuvant endocrine treatment and relapse within 12 months of stopping this treatment, this can be considered a resistance to this agent) endocrine treatment for metastatic disease being either tamoxifen or any aromatase inhibitor (AI), with patients still considered to be suitable candidates for a third line endocrine treatment, 7) Superficial measurable lesions will be included as measurable, provided it is photographed, 8) Patients need to be on this endocrine treatment for at least three months in order to clearly document endocrine resistance and exclude as much as possible late responses, 9) Disease progression has to documented on consecutive radiological examinations or photographs (excluding ultrasound and PET), 10) Adequate bone marrow reserve WCC > 3.0x109/L, ANC > 1.5x109/L, PLTs> 100x109/L, Hb >10gr/dL, 11) Normal liver function defined by a bilirubin < 1.25 x ULN and transaminases < 3 x ULN, 12) Life expectancy > 6 months, 13) One line of chemotherapy for metastatic disease is allowed provided this was not the last treatment received prior to study entry, 14) No peripheral neuropathy > grade 1, 15) No other life-threatening disease,
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E.4 | Principal exclusion criteria |
1) Non-measurable disease as sole disease sites as defined by RECIST, 2) More than one line of chemotherapy for metastatic disease, 3) Prior radiotherapy within two weeks prior to study entry, 4) Surgery within two weeks prior to study entry, 5) Other invasive cancer diagnosis within 5 years prior to study entry, 6) Severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis, 7) Uncontrolled diabetes mellitus, (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug, 8) Pregnant or breast feeding, 9) Neuropathy > or = grade II, 10) Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used 11) Serious medical or psychiatric conditions that precludes participation in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is that in this group of 28 patients, 14 in each group, at least 7% of patients should obtain clinical benefit (SD+PR+CR). If we are unable to demonstrate that the clinical benefit rate is at least 7%, this regimen should not be considered for further testing. |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
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 | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 35 |
E.8.9.2 | In all countries concerned by the trial days | 35 |