E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Female patients with histologically proven metastatic or locally advanced breast cancer who have HER-2 overexpression in the primary tumour and/or a metastatic lesion. |
|
MedDRA Classification |
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 |
The primary objective of the trial is to demonstrate evidence of clinical efficacy of HER-2 Protein AutoVac(TM)/QS-21, that is the number of evaluable patients with evidence of clinical benefit, defined as: • A complete response (CR) or partial response (PR), or • Stable disease (SD) for at least 6 months (26 weeks).
|
|
E.2.2 | Secondary objectives of the trial |
• To obtain data on the immune response following long-term treatment. • To obtain safety data on long-term use.
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Histological proven adenocarcinoma of the breast. • Locally advanced or metastatic disease. • Centrally confirmed HER-2 overexpression by either a score 3+ by DAKO HercepTest TM(DakoCytomation) or a positive DAKO HER2 FISH pharmDx TM (DakoCytomation) test result on either the primary tumour or metastasis. • At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST). • Age more than or equal to 18 years and less than or equal to 80 years. • Life expectancy more than or equal to 6 months. • An Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1. • Signed written informed consent prior to trial entry. • Willing and able to comply with the protocol for the duration of the trial. • No more than two prior chemotherapy regimens for locally advanced/metastatic disease (adjuvant chemotherapy after primary therapy is not counted as a regimen). • No more than three prior lines of endocrine treatment for locally advanced/metastatic disease
|
|
E.4 | Principal exclusion criteria |
• Women of child-bearing potential not using a reliable and appropriate contraceptive method. Pregnant and lactating women. Women of childbearing potential with either a positive or no pregnancy test at screening. • Patients who have received chemotherapy or other immunosuppressive therapy within 4 weeks prior to start of study treatment. • Patients who have received hormonal therapy within 4 weeks of starting study treatment. • Radiotherapy involving more than 25% of the bone marrow given within 3 months before inclusion in the study. • Patients who have previously been treated at any time with any HER-2 based anticancer vaccine. • Patients who have been treated with any other anticancer vaccine within 1 year of starting study treatment. • Patients who have previously been treated with Herceptin® (trastuzumab) or any other agents, commercially available or investigational, that target the HER-2 axis. • Concurrent immunosuppressive therapy, including, but not limited to, low dose methotrexate or cyclophosphamide, corticosteroids (with the exception of topically applied/inhaled steroids). Concurrent anti-tumour treatment. • Other cancers than breast cancer, except for basal cell carcinoma of the skin and in situ carcinoma of cervix. • Patients with history of significant cardiovascular disease or left ventricular ejection fraction (LVEF) <50%, determined by echocardiogram or multiple gated acquisition (MUGA) scans. • Uncontrolled hypertension. • Participation in another clinical trial with an investigational agent within 30 days preceding initiation of treatment. • Known infection of human immunodeficiency virus (HIV). • History of or co-existing severe auto-immune diseases or other diseases which qualify as auto-immune in origin. • Significantly impaired immune function as judged by the investigator. • Patients with abnormal baseline haematology values, abnormal baseline liver function tests, known renal dysfunction or abnormal serum creatinine values. • A history or clinical evidence of central nervous system (CNS) metastases. • Any other serious medical, social or mental condition which, in the opinion of the investigator, would be detrimental to the patient or the trial.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the trial is clinical benefit rate, defined as •Complte Response or Partial Response, or •Stable Disease for at least 6 months (26 weeks) (RECIST criteria). |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Kinetics of the immune response |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
A two-stage Phase II trial |
|
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 | 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.8.5 | 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 | 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 | Information not present in EudraCT |
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
| |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |