Comparison of the efficacy of Denosumab when administered only every 12 weeks instead of every 4 weeks related to the prevention of complications on the bone skeleto

Phase 1

Conditions: Bone metastases from castration resistant prostate cancer or from breast cancer
MedDRA version: 20.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001189-87-AT

Lead Sponsor: Swiss Group for Clinical Cancer Research

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 1380

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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1380
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1380

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: not applicable;Primary end point(s): Time to first on-trial symptomatic skeletal event (SSE; clinically significant pathological fracture, radiotherapy to bone or spinal cord compression).;Timepoint(s) of evaluation of this end point: Week 1 (Baseline) and than every twelve weeks over five years

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 1. Toxicity (Focus on hypocalcemia and osteonecrosis of the jaw)<br> 2. Time to first and subsequent on-trial SSE<br> 3. Overall survival (OS)<br> 4. Quality of life (QoL)<br> 5. Skeletal morbidity period rate (SMPR)<br> 6. Skeletal morbidity rate (SMR)<br> 7. Health economic analysis<br> 8. Bone turnover markers<br> ;Timepoint(s) of evaluation of this end point: Week 1 (Baseline) and than every twelve weeks over five years

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