E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypercalcemia of Malignancy (HCM) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020588 |
E.1.2 | Term | Hypercalcemia of malignancy |
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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 |
• This proof-of-concept study is designed to evaluate the potential for denosumab to treat HCM that does not respond to recent treatment with Intravenous (IV) bisphosphonates by lowering corrected serum calcium (CSC) ≤ 11.5 mg/dL (2.9 mmol/L) by study day 10. |
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E.2.2 | Secondary objectives of the trial |
• To determine the duration of the treatment effect • To determine the time to response • To determine the time to relapse • Changes in CSC level from baseline • To determine the safety of denosumab in this subject population |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Hypercalcemia of Malignancy (HCM) as defined as documented histologically or cytologically confirmed cancer and a CSC > 12.5 mg/dL (3.1 mmol/L) at screening by local laboratory • Last IV bisphosphonate treatment must be ≥ 7 days and ≤ 30 days before the screening CSC • Adults (≥ 18 years) • Adequate organ function as defined by the following criteria: - serum aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) - serum alanine aminotransferase (ALT) ≤ 5 x ULN - serum total bilirubin ≤ 2 x ULN • Before any study-specific procedure is performed, the appropriate written informed consent must be obtained |
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E.4 | Principal exclusion criteria |
• Evidence of hyperparathyroidism, hyperthyroidism, adrenal insufficiency, vitamin D intoxication, milk alkali syndrome, sarcoidosis, or other granulomatous disease • Receiving dialysis for renal failure • 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 • Prior administration of denosumab • Treatment with thiazides, calcitonin, mithramycin, and gallium nitrate within 7 days prior to the date of the screening CSC • Treatment with cinacalcet within 4 weeks prior to the date of the screening CSC • Thirty days or less since receiving an investigational product or device (ie, does not have marketing authorization; thalidomide use is allowed) in another clinical study • Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products) • Female subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment • Subject (male or female) is not willing to use 2 highly effective methods of contraception during treatment and for 7 months (female) or 10 months (male) after the end of treatment • Male subject with a pregnant partner who is not willing to use a condom during treatment and for additional 10 months after the end of treatment • Subject will not be available for follow-up assessment. • 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with a response, defined as CSC ≤ 11.5 mg/dL (2.9 mmol/L), within 10 days after the first dose of denosumab. |
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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 | No |
E.8.1.2 | Open | No |
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 | No |
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.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 | 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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The end of study will occur 4 weeks after the last dose of denosumab. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |