E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Giant Cell Tumor (GCT) of Bone |
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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 | 10005968 |
E.1.2 | Term | Bone giant cell tumor |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety profile of denosumab in subjects with GCT of bone |
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E.2.2 | Secondary objectives of the trial |
- Evaluation of time to disease progression in subjects with unsalvageable GCT treated with denosumab - Evaluation of the proportion of subjects able to undergo limb or joint sparing (eg, curettage) surgical procedures in denosumab treated subjects with salvageable GCT who would have otherwise required en bloc excision |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Pathologically confirmed giant cell tumor of bone within 1 year before study enrollment - Measurable evidence of active disease within 1 year before study enrollment - Subjects with surgically unsalvageable disease (eg, sacral, spinal GCT, or multiple lesions including pulmonary metastases) OR subjects whose planned initial surgery includes joint resection, limb amputation, hemipelvectomy or surgical procedure resulting in severe morbidity, other than curettage with complete resection of tumor - Karnofsky performance status ≥ 50% (ie, ECOG status 0, 1, or 2) - Adults - Before any study-specific procedure is performed, the appropriate written informed consent must be obtained.
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E.4 | Principal exclusion criteria |
- Currently receiving other GCT specific treatment (eg, radiation, chemotherapy, or embolization) - Concurrent bisphosphonate treatment - Known or suspected current diagnosis of underlying malignancy including high-grade sarcoma, osteosarcoma, fibrosarcoma, malignant giant cell sarcoma - Known or suspected current diagnosis of non GCT giant cell-rich tumors - Known or suspected current diagnosis of brown cell tumor of bone - Known diagnosis of second malignancy within the past 5 years - 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 for the course of the study - Women or men unwilling to use adequate contraceptive measures - Thirty days or less since receiving an investigational product - Subject has known sensitivity to any of the products to be administered during dosing - Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the safety profile of denosumab characterized in terms of the type, frequency, and severity of adverse events and laboratory abnormalities for each cohort of the study. |
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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 | No |
E.8.1.2 | Open | Yes |
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 | No |
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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 (end of follow-up for all subjects) will occur approximately 54 months after the start of enrollment. Each subject will have an end of study visit approximately 4 weeks after their last dose of study drug. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |