E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of bone metastases in subjects with advanced cancer excluding breast and prostate cancer or multiple myeloma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027452 |
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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 determine if denosumab is non-inferior to zoledronic acid with respect to the first on-study occurrence of a skeletal related event SRE in subjects with advanced cancers and bone metastases |
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E.2.2 | Secondary objectives of the trial |
To determine if denosumab is superior to zoledronic acid with respect to the first on-study SRE To determine if denosumab is superior to zoledronic acid with respect to the first-and-subsequent on-study SRE multiple event analysis To compare the treatment effect of denosumab with zoledronic acid on pain To compare the treatment effect of denosumab with zoledronic acid on the first on-study use of radiation to bone To assess the safety and tolerability of denosumab compared with zoledronic acid |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
adult with histologically or cytologically confirmed advanced cancers including solid tumors, multiple myeloma, and lymphoma current or prior radiographic ie, x-ray, computer tomography CT , or magnetic resonance imaging MRI evidence of at least 1 bone metastasis or bone lesion from multiple myeloma Eastern Cooperative Oncology Group ECOG performance status of 0, 1, or 2 adequate organ function as defined by the following criteria 56256; 56451; serum aspartate aminotransferase AST 8804; 5 x upper limit of normal ULN 56256; 56451; serum alanine aminotransferase ALT 8804; 5 x ULN 56256; 56451; serum total bilirubin 8804; 2 x ULN 56256; 56451; creatinine clearance Cockcroft-Gault 8805; 30 mL/min 56256; 56451; albumin-adjusted serum calcium 8805; 2.0 mmol/L 8.0 mg/dL and 8804; 2.9 mmol/L 11.5 mg/dL Before any study-specific procedure is performed, the appropriate written informed consent must be obtained |
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E.4 | Principal exclusion criteria |
diagnosis of breast or prostate cancer current or prior IV bisphosphonate administration current or prior oral bisphosphonate for the treatment of bone metastasis / osteolytic lesion planned radiation therapy or surgery to bone prior administration of denosumab known brain metastases life expectancy less than 6 months prior history or current evidence of osteonecrosis/osteomyelitis of the jaw active dental or jaw condition which requires oral surgery non-healed dental/oral surgery planned invasive dental procedure over the course of the study evidence of any of the following conditions per subject self report or medical chart review any other prior malignancy other than basal cell carcinoma or in situ cervical cancer with active disease within 3 years before randomization 56256; 56451; known infection with human immunodeficiency virus 56256; 56451; active infection with Hepatitis B virus or Hepatitis C virus any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results thirty days or less since receiving an investigational product or device ie, does not have marketing authorization in another clinical trial pregnant or breast feeding women subject with reproductive potential who will not agree to use effective contraception as defined by the principal investigator or designee 56256; 56451; known sensitivity to any of the products to be administered during the study eg, zoledronic acid, mammalian derived products, calcium or vitamin D |
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E.5 End points |
E.5.1 | Primary end point(s) |
time to the first on-study SRE non-inferiority |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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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 | |
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 |