E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast cancer patients with bone dominant disease who have progressed on endocrine therapy and are no longer considered suitable for further endocrine therapy |
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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 | 10027452 |
E.1.2 | Term | Metastases to bone |
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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 if multiple intravenous injections of Alpharadin have any clinically relevant effect on bone markers in breast cancer patients with bone dominant disease who have progressed on endocrine therapy and are no longer considered suitable for endocrine therapy. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety of multiple intravenous injections of Alpharadin • To evaluate potential benefit, palliative and/or anti-tumour effect of Alpharadin • To evaluate long term-radiation toxicity
Exploratory Objective: • To determine the metabolic effects on bone metastases as a result of Alpharadin treatment. • To determine the change in number of circulating tumour cells (CTC) as a result of Alpharadin treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is female, and either post-menopausal (cessation of menses for more than 1 year) or surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy) or in therapy-induced premature menopause with LHRH agonists. If of childbearing potential the result of a urine human chorionic gonadotropin pregnancy test, performed on the same day as and with the result known before study drug administration, must be negative. 2. Histological or cytological evidence of primary breast cancer. 3. Bone dominant disease (with or without metastases in soft tissue, lymph nodes and/or skin) with at least one non-irradiated bone metastasis on planar bone scintigraphy/SPECT ± CT within previous the 12 weeks. 4. Patient has unequivocally progressed on endocrine therapy and further benefit from endocrine therapy is considered unlikely (progression must be documented based on imaging and/or other clinically relevant information). 5. Patient has been on bisphosphonate therapy for at least 3 months prior to treatment start and no change to bisphosphonate therapy is expected during the treatment phase of the study. 6. Latest endocrine therapy stopped at least 2 weeks prior to treatment start. 7. ECOG PS 0 – 2. 8. Life expectancy ≥6 months. 9. Patient fulfils the following laboratory requirements: • White Blood Cell Count (WBC) ≥3,000/mm3 • Absolute Neutrophil Count (ANC) ≥1,500/mm3 • Platelet (PLT) count ≥100,000/mm3 • Haemoglobin (HGB) ≥9 g/dl • Bilirubin ≤2.0 mg/dl • Aspartate aminotransferase (AST) and Alkaline aminotransferase (ALT) ≤3 times upper institutional limit of the normal range • Serum creatinine ≤2.0 mg/dl • Urine NTX ≥20 nmol/mmol creatinine 10. Patient must be able and willing to sign an informed consent form indicating that she is aware of the investigational nature of this study in keeping with the policies of the institution, and must have provided written authorisation for use and disclosure of protected health information. 11. Patient must be willing and able to comply with the protocol and agree to return to the hospital for follow-up visits and examination.
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E.4 | Principal exclusion criteria |
1. Received an investigational drug within 4 weeks prior to the administration of Alpharadin, or is scheduled to receive one during the treatment period. 2. Received chemotherapy, immunotherapy, or external beam radiation therapy within the last 4 weeks prior to administration of study drug, or has not recovered from acute adverse reactions (ARs) as a result of such therapy. 3. Is likely to require chemotherapy or immunotherapy within the 16 weeks treatment period. 4. Presence of imminent or established spinal cord compression based on clinical findings and/or Magnetic Resonance Imaging (MRI). 5. Presence of other currently active (relapse within the last 3 years) malignancy (except non melanoma skin cancer) that are not breast cancer metastases. 6. Presence of unequivocal visceral metastases. Brain metastases are allowed only if well controlled and if not associated with symptoms. Treatment for brain metastasis should have been completed at least 8 weeks prior to treatment start. 7. Patients with any other serious illness or medical condition, such as: • Any uncontrolled infection • Clinical heart failure severe enough to cause marked limitation of activity, and who is only comfortable at rest; or heart failure more severe than this (New York Heart Association (NYHA) Heart Failure Class III or IV) • Crohn’s disease or ulcerative colitis • Bone marrow myelodysplasia • Unmanageable faecal incontinence
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the effect of Alpharadin on changes in urine levels of NTX (uNTX) and serum bone specific alkaline phosphatase (bALP) at 16 weeks. |
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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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |