E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bone metastases from castration resistant prostate cancer or from breast cancer |
Knochenmetastasen von kastrationsresistentem Prostatakrebs oder Brustkrebs |
|
E.1.1.1 | Medical condition in easily understood language |
Breast cancer or prostate cancer with complications on the bone skeleton |
Brust- oder Prostatakrebs mit Komplikationen am Knochenskelett |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 main objective is to establish that denosumab 120 mg given every twelve weeks is non-inferior to denosumab 120 mg given every four weeks. |
Die Hypothese dieser Studie ist, dass 120 mg Denosumab verabreicht alle zwölf Wochen vergleichbar wirksam ist (non inferior) mit 120 mg Denosumab verabreicht alle vier Wochen. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent 2. ECOG Performance 0-2 3. Age ≥ 18 years 4. Confirmed diagnosis of breast or prostate cancer before randomization. 5. Patient has metastatic breast cancer (stage IV, all subtypes allowed except small cells) or prostate cancer (stage IV, exception: small cells) and bone metastases and is planned to receive or is receiving antineoplastic treatment. 6. Patients with prostate cancer must have evidence of disease Progression on continuous androgen deprivation therapy (CRPC). 7. Patients must have ≥ three bone metastases (lytic or blastic or mixed). 8. Corrected serum calcium ≥ 2 mmol/l and ≤ 3 mmol/l (medical treatments to obtain serum calcium levels in the normal range are allowed, as far as no denosumab is used. Maximally one dose of bisphosphonates in the case of hypercalcemia is allowed, if the bisphosphonate was applied at least three weeks before the first dose of denosumab). 9. Liver transaminases not more than 1.5 x ULN or not more that 3 x ULN with liver metastases. Serum total bilirubin ≤ 1.5 x ULN (≤ 2.0 x ULN in case of known Gilbert's disease). |
|
E.4 | Principal exclusion criteria |
1. Definite contraindication for denosumab (e.g. hypocalcemia [Albumin-corrected serum calcium < 2.0 mmol/l]). 2. History or current evidence of osteonecrosis of the jaw (ONJ). 3. Non-healed mucosa in oral cavity (by surgery or as a side effect of any other Treatment). 4. Jaw or dental conditions that require oral surgery or if surgery or invasive dental procedures are planned. 5. Prior use of denosumab for bone metastases or bisphosphonates to treat bone metastases. Patients treated with denosumab or bisphosphonates against osteopenia or osteoporosis are followed to enter the trial if the last dose was more than 28 days before randomization. 6. Patients with known osteoporosis (T-score ≤ -2.5) at study entry. 7. Radiotherapy or surgery to the bone within the last two weeks before randomization or planned within six weeks after randomization. 8. Presence or history of CNS metastases or leptomeningeal disease. A MRI Evaluation within twelve weeks before randomization must be performed in case of suspicious symptoms.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to first on-trial symptomatic skeletal event (SSE; clinically significant pathological fracture, radiotherapy to bone or spinal cord compression). |
Zeit bis zum ersten Auftreten eines symptomatischen skelletalen Ereignisses innerhalb der Studie (klinisch signifikante pathologische Fraktur, Radiotherapie des Knochens, chirurgischer Eingriff am Knochen oder Rückenmarkskompression). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 1 (Baseline) and than every twelve weeks over five years |
Woche 1 (Baseline) anschließend alle zwölf Wochen über fünf Jahre |
|
E.5.2 | Secondary end point(s) |
1. Toxicity (Focus on hypocalcemia and osteonecrosis of the jaw) 2. Time to first and subsequent on-trial SSE 3. Overall survival (OS) 4. Quality of life (QoL) 5. Skeletal morbidity period rate (SMPR) 6. Skeletal morbidity rate (SMR) 7. Health economic analysis 8. Bone turnover markers |
1. Toxizität 2. Zeit bis zum ersten und nachfolgenden SSE innerhalb der Studie 3. Gesamtüberleben 4. Lebensqualität 5. “Skeletal morbidity period rate” (SMPR; Skelett Morbiditäts-Perioden Rate) 6. “Skeletal morbidity rate” (SMR; Skelett Morbiditätsrate) 7. Gesundheitsökonomische Marker 8. Knochenumsatz-Marker |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 1 (Baseline) and than every twelve weeks over five years |
Woche 1 (Baseline) anschließend alle zwölf Wochen über fünf Jahre |
|
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 | No |
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 | Yes |
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) | 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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Denosumab appliziert alle zwölf Wochen |
Denosumab administered every twelve weeks |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 | No |
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
|
LPLV - last patient last visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
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 | 10 |