| 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), 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 | The secondary objectives of the trial are:
·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 | Female breast cancer patients who fulfil the following criteria will be eligible for inclusion in the trial:
1.Histological proven adenocarcinoma of the breast.
2.Locally advanced or metastatic disease.
3.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. The HER-2 expression status of the patient MUST BE confirmed by the central laboratory before enrolment and the patient’s first vaccination with HER-2 Protein AutoVac(TM).
4.At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST).
5.Age less than or equal to 18 yearsand less than or equal to 80 years
6.Life expectancy more than or equal to 6 months.
7.Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
8.Signed written informed consent prior to trial entry.
9.Willing and able to comply with the protocol for the duration of the trial.
10.No more than two prior chemotherapy regimens for locally advanced/metastatic disease (adjuvant chemotherapy after primary therapy is not counted as a regimen).
11.No more than three prior lines of endocrine treatment for locally advanced/metastatic disease.
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| E.4 | Principal exclusion criteria | Patients will be excluded from the trial should they meet one or more of the following criteria:
1.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.
2.Patients who have received chemotherapy or other immunosuppressive therapy within 4 weeks prior to start of study treatment.
3.Patients who have received hormonal therapy within 4 weeks of starting study treatment.
4.Radiotherapy involving more than 25% of the bone marrow given within 3 months before inclusion in the study.
5.Patients who have previously been treated at any time with any HER-2 based anticancer vaccine.
6.Patients who have been treated with any other anticancer vaccine within 1 year of starting study treatment.
7.Patients who have previously been treated with Herceptin® (trastuzumab) or any other agents, commercially available or investigational, that target the HER-2 axis.
8.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.
9.Other cancers than breast cancer, except for basal cell carcinoma of the skin and in situ carcinoma of cervix.
10.Patients with history of significant cardiovascular disease or left ventricular ejection fraction (LVEF) less than 50%, determined by echocardiogram or multiple gated acquisition (MUGA) scans.
11.Uncontrolled hypertension.
12.Participation in another clinical trial with an investigational agent within 30 days preceding initiation of treatment.
13.Known infection of human immunodeficiency virus (HIV).
14.History of or co-existing severe auto-immune diseases:
-Auto-immune neutropaenia.
-Auto-immune thrombocytopaenia.
-Haemolytic anaemia.
-Systemic lupus erythematosus.
-Sjogren syndrome.
-Scleroderma.
-Myasthenia gravis.
-Goodpasture syndrome.
-Addison’s disease.
-Hashimoto’s thyroiditis.
-Active Graves’ disease.
-Other diseases which qualify as auto-immune in origin.
14.Significantly impaired immune function as judged by the investigator.
15.Patients with any of the following abnormal baseline haematology values:
-Haemoglobin less than 10 g/dL (6.2 mmol/L).
-White blood cells (leukocytes) less than 3 x 109/L.
-Lymphocytes less than 1 x 109/L.
-Platelets less than 100 x 109/L.
16.Patients with any of the following abnormal baseline liver function tests:
-Serum bilirubin more than 1.5 x upper normal limit (UNL), except if the patient has a documented diagnosis of Gilbert’s syndrome.
-g-Glutamyltransferase (GGT) more than 2.5 x UNL (or 5 x UNL in case of liver metastases).
-Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 2.5 x UNL (or 5 x UNL in case of liver metastases).
17.Known renal dysfunction or the following abnormal baseline values:
-Serum creatinine more than 1.5 x UNL.
18.A history or clinical evidence of central nervous system (CNS) metastases.
19.Any other serious medical, social or mental condition which, in the opinion of the investigator, would be detrimental to the patient or the trial.
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| E.5 End points |
| E.5.1 | Primary end point(s) | The primary endpoint of the trial is clinical benefit rate, defined as:
·Clinical Response or Partial Response, or
·Stable Disease for at least 6 months (26 weeks).
| |
| 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | | Kinetics of the immunological response | |
| 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 | No |
| 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 | | The trial will be stopped when the last patient included reaches 26 weeks or when the last ongoing patient has been in the trial for at least 26 weeks or when all patients have discontinued treatment, whichever occurs first. | |
| 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 |
