SAKK 96/12 - Prevention of symptomatic complications in the skeleton with Denosumab administered every 4 weeks versus every 12 weeks

Austria, Germany, Switzerland (ICTRP)

ID di studio ICTRP
NCT02051218 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
non disponibile

Titolo accademico
Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks - A Non-Inferiority Phase III Trial (ICTRP)

Titolo pubblico
Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks (ICTRP)

Malattie studiate
Metastatic Breast CancerMetastatic Prostate CancerBone Metastases (ICTRP)

Intervento studiato
Drug: Denosumab (reduced dosing)Drug: Denosumab (standard dosing) (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Supportive Care. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Inclusion Criteria:

- Patient has given written informed consent.

- Histologically confirmed diagnosis of breast or prostate cancer before
randomization.

- Patient has metastatic breast cancer (stage IV, all subtypes allowed) or prostate
cancer (stage IV) and bone metastases and is planned to receive or is receiving
antineoplastic treatment.

- Patients with prostate cancer must have evidence of disease progression on
continuous androgen deprivation therapy (CRPC).

- Patients must have = 3 bone metastases (lytic or blastic or mixed). The lesions must
be documented by radiological evaluation within 12 weeks before randomization (by
X-Ray, CT scan, PET-CT, MRI scan or bone scintigraphy).

- WHO performance status 0-2

- Age = 18 years.

- 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 1 dose of bisphosphonates in the case of hypercalcemia is allowed,
if the bisphosphonate was applied at least 3 weeks before the first dose of
denosumab).

- Liver transaminases not more than 1.5 x ULN or not more than 3 x ULN with liver
metastases. Serum total bilirubin = 1.5 x ULN (= 2.0 x ULN in case of known
Gilbert's disease)

- Women are not breastfeeding. Women with child-bearing potential are using effective
contraception, are not pregnant and agree not to become pregnant during
participation in the trial and during the 12 months thereafter. A negative pregnancy
test before inclusion (within 7 days) into the trial is required for all women with
child-bearing potential.

- Men agree not to father a child during participation in the trial and during 12
months thereafter.

Exclusion Criteria:

- Definite contraindication for denosumab (e.g. hypocalcaemia [Albumin-corrected serum
calcium < 2.0 mmol/l]).

- History or current evidence of osteonecrosis of the jaw.

- Non-healed mucosa in oral cavity (by surgery or as a side effect of any other
treatment).

- Jaw or dental conditions that require oral surgery or if surgery or invasive dental
procedures are planned.

- Prior use of denosumab for bone metastases (dose 120 mg every 4 weeks) or
bisphosphonates to treat bone metastases. Patients treated with denosumab or
bisphosphonates against osteopenia or osteoporosis are allowed to enter the trial if
the last dose was more than 28 days before randomization.

- Patients with known osteoporosis (T-score = -2.5) at study entry (since fractures
from osteoporosis are difficult to be discriminated from fractures through bone
metastases).

- Radiotherapy or surgery to the bone within the last two weeks before randomization
or planned within 6 weeks after randomization.

- Presence or history of CNS metastases or leptomeningeal disease. A MRI evaluation
within 12 weeks before randomization must be performed in case of suspicious
symptoms.

- Psychiatric disorder precluding understanding of information on trial related
topics, giving informed consent, filling out QoL forms.

- Concurrent treatment in a clinical trial with SSE or SRE as primary endpoint.

- Known hypersensitivity to trial drug or hypersensitivity to any other component of
the trial drug (e.g. fructose).

- Any concomitant drugs contraindicated for use with the trial drugs according to the
approved product information.

- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the trial protocol. (ICTRP)

non disponibile

Endpoint primari e secondari
Time to first on-trial symptomatic skeletal event (SSE; Clinically significant pathological fracture, radiation therapy to bone, surgery to bone or spinal cord compression). (ICTRP)

Quality of Life measured by FACT-G and FACT-BP;Skeletal morbidity period rate (SMPR);Skeletal morbidity rate (SMR);Health economic analysis;Bone turnover markers;Overall Survival (OS);Toxicity (focus on hypocalcaemia and osteonecrosis of the jaw);Time to first and subsequent on-trial SSE (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Roger von Moos, PD MD;Arnoud Templeton, MD;Silke Gillessen, Prof;Andreas M?ller, MD, Kantonsspital Graub?nden,Cantonal Hospital of St. Gallen,Cantonal Hospital of St. Gallen,Kantonsspital Winterthur KSW (ICTRP)

ID secondari
000000685, 2014-001189-87, SAKK 96/12 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT02051218 (ICTRP)