Content - SAKK 96/12

SAKK 96/12 - Treatment of patients with bone metastases using Xgeva®

Treatment of patients with bone metastases using Xgeva® - Prevention of symptomatic skeletal complications with denosumab administered every 4 weeks versus every 12 weeks.

Bone metastases – the spread of cancer to the bones – are a frequent complication in patients with advanced cancer, and new cases are diagnosed in Switzerland in more than 5000 people a year. Since it was granted marketing approval in December 2011, Xgeva® has been increasingly used for the treatment of patients with bone metastases.

The project SAKK 96/12 is designed to show that less frequent dosing of Xgeva® is at least as effective as the approved standard dosing regimen. The project was launched because trial data have prompted the approved therapy with Xgeva® to be questioned with regard to dosing, toxicity and cost/benefit ratio. This study will closely monitor not only efficacy, but also side effects and quality of life, because it is assumed that less frequent dosing will lead overall to fewer side effects and thus also a better quality of life.

Since the rising costs in healthcare and the cost-effectiveness of medical treatment are leading to ever greater challenges for society, a further objective of this project is to examine the health economic aspects. The project SAKK 96/12 is being carried out in collaboration with the health insurers.

Study Chairs:

Prof. Dr. med. Roger von Moos, Cantonal Hospital of Graubünden, +41 81 256 66 47

PD Dr. med. Arnoud Templeton,  Cantonal Hospital of St.Gallen, +41 61 685 8330

Prof. Dr. med. Silke Gillessen, Cantonal Hospital of St.Gallen, +41 71 494 10 92

Dr. med. Andreas Müller, Cantonal Hospital of Winterthur, +41 52 266 25 52

  • Contacts at the hospitals

  • 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.

Locations for this trial:

Hirslanden Klinik Aarau
Schänisweg
0 5001 Aarau
Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Kantonsspital Baden
Im Ergel 1
4600 Baden
Brustzentrum Basel - Bethesda Spital
Gellertstrasse 144
0 4002 Basel
St. Claraspital AG
Kleinriehenstrasse 30
0 4058 Basel
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Lindenhofgruppe, Engeriedspital
Riedweg 15
0 3012 Bern
Spitalzentrum Biel
Vogelsang 84
0 2501 Biel
Spitalzentrum Oberwallis
Ueberlandstrasse 14
0 3902 Brig
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Spital Thurgau, Kantonsspital Münsterlingen
Spitalcampus 1
0 8596 Münsterlingen
Hôpital Fribourgeois HFR
Chemin des Pensionnats 2
1708 1708 Fribourg
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
CCAC Centre de Chimiothérapie Anti-Cancéreuse
Avenue d'Ouchy 35
0 1006 Lausanne
Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Kantonsspital Liestal
Rheinstrasse 26
0 4410 Liestal
Fondazione Oncologia Lago Maggiore
Via Antonio Ciseri 19
0 6600 Locarno
Oncologia Varini & Calderoni & Christinat
Via Antonio Fogazzaro 3
0 6900 Lugano
Hirslanden Klinik St. Anna Luzern
Sankt-Anna-Strasse 32
0 6006 Luzern
Kantonsspital Luzern
Spitalstrasse
0 6000 Luzern
Spital Thurgau, Kantonsspital Frauenfeld
Waldeggstrasse 8A
0 8501 Frauenfeld
Kantonsspital Olten
Baslerstrasse 150
0 4600 Olten
Hôpital du Valais Sion
Avenue du Grand-Champsec 80
0 1951 Sion
Solothurner Spitäler AG (soH)
Schöngrünstrasse 42
0 4500 Solothurn
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Tumor- und Brustzentrum ZeTuP St.Gallen
Rorschacher Strasse 150
0 9006 St.Gallen
Spital STS AG Thun
Krankenhausstrasse 12
0 3600 Thun
Kantonsspital Winterthur
Brauerstrasse 15
0 8401 Winterthur
Brustzentrum Seefeld
Seefeldstrasse 214
0 8008 Zürich
Klinik Hirslanden Zürich
Witellikerstrasse 40
0 8032 Zürich
Klinik Hirslanden im Park
Seestrasse 259
0 8002 Zürich
Spital Limmattal
Urdorferstrasse 100
0 8952 Schlieren
Stadtspital Triemli
Birmensdorferstrasse 497
0 8063 Zürich
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich
Hôpital neuchâtelois
Chasseral 20
0 2303 La Chaux-de-Fonds
Universitaetsklinikum Düsseldorf
Moorenstraße 5
0 Düsseldorf 40225