Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks

NCT02051218 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: SAKK 96/120000006852014-001189-87
• Study Type: interventional
• Target: 1,380
• Locations: 3 countries
• Sites: 50

Brief Summary

The aim of the trial is to test the hypothesis that the benefit of denosumab is maintained if administered only every 12 weeks as compared to every 4 weeks.

Conditions

Metastatic Breast Cancer; Metastatic Prostate Cancer; Bone Metastases

Keywords

metastatic breast cancer; castration resistant metastatic prostate cancer; bone metastases; Denosumab; XGEVA; de-escalation

Outcome Measures

Primary Outcomes (1)

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

  A SSE is defined as one of the following events: Clinically significant pathological fracture, radiation therapy to bone, surgery to bone, or spinal cord compression.

  at the latest 5 years after randomization.

Secondary Outcomes (8)

• Toxicity (focus on hypocalcaemia and osteonecrosis of the jaw)

  at the latest 5 years after randomization.

• Time to first and subsequent on-trial SSE

  at the latest 5 years after randomization.

• Quality of Life measured by FACT-G and FACT-BP

  at the latest 5 years after randomization.

• Skeletal morbidity period rate (SMPR)

  at the latest 5 years after randomization.

• Skeletal morbidity rate (SMR)

  at the latest 5 years after randomization.

Study Arms (2)

Arm A (standard arm)

ACTIVE COMPARATOR

Denosumab 120mg (XGEVA®) sc. q4w

Drug: Denosumab (standard dosing)

Arm B (reduced arm)

EXPERIMENTAL

Denosumab 120mg (XGEVA®) sc. q4w \[weeks 1, 5, 9\] followed by Denosumab 120mg (XGEVA®) sc. q12w \[weeks 13, 25, …\]

Drug: Denosumab (reduced dosing)

Interventions

Denosumab (reduced dosing) DRUG

3x Denosumab 120mg (XGEVA®) sc. q4w followed by Denosumab 120mg (XGEVA®) sc. q12w

Also known as: XGEVA®

Arm B (reduced arm)

Denosumab (standard dosing) DRUG

Denosumab 120mg (XGEVA®) sc. q4w

Also known as: XGEVA®

Arm A (standard arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (50)

Landeskrankenhaus Feldkirch

Feldkirch, 6800, Austria

Location

Klinikum Wels-Grieskrichen GmbH

Wels, 4600, Austria

Location

Uniklinik Düsseldorf, Urologische Klinik

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Düsseldorf, Frauenheilkunde/Geburtshilfe

Düsseldorf, 40225, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Universitäts-Frauenklinik Ulm

Ulm, 89075, Germany

Location

Hirslanden Klinik Aarau

Aarau, CH-5001, Switzerland

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

Brustzentrum Basel - Praxis für ambulante Tumortherapie

Basel, 4052, Switzerland

Location

St. Claraspital AG

Basel, CH-4016, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Klinik Engeried / Praxis Oncocare

Bern, 3012, Switzerland

Location

Inselspital, Bern

Bern, CH-3010, Switzerland

Location

Spitalzentrum Biel

Biel, CH-2501, Switzerland

Location

Spitalzentrum Oberwallis

Brig, 3900, Switzerland

Location

Centre du Sein de Genève, Clinique des Grangettes

Chêne-Bougeries, 1224, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Kantonsspital Frauenfeld - Brustzentrum

Frauenfeld, 8501, Switzerland

Location

Hopital Fribourgeois

Fribourg, 1708, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1211, Switzerland

Location

Clinique De Genolier

Genolier, 1272, Switzerland

Location

Hôpital neuchâtelois

La Chaux-de-Fonds, 2300, Switzerland

Location

CCAC Lausanne

Lausanne, 1004, Switzerland

Location

CHUV

Lausanne, 1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Fondazione Oncologia / Oncologia ematologia

Locarno, 6600, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Hirslanden Klinik St. Anna Luzern

Lucerne, 6006, Switzerland

Location

Oncologia Varini & Calderoni & Christinat

Lugano, 6900, Switzerland

Location

Onkologie Zentrum Spital Männedorf

Männedorf, 8708, Switzerland

Location

Kantonsspital Muensterlingen

Münsterlingen, 8596, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Tumor and Brustzentrum Ostschweiz TBZO

Sankt Gallen, 9016, Switzerland

Location

Tumor and Brustzentrum Ostschweiz TBZO

Sankt Gallen, CH-9006, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Rundum Onkologie am Bahnhofpark

Sargans, 7320, Switzerland

Location

Spital Limmattal

Schlieren, 8952, Switzerland

Location

Hôpital du Valais Sion

Sion, 1951, Switzerland

Location

Bürgerspital Solothurn - Zentrum für Onkologie und Hämatologie

Solothurn, 4500, Switzerland

Location

Spital STS AG

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Onkologie Bellevue

Zurich, 8001, Switzerland

Location

Brustzentrum-Zürich

Zurich, 8005, Switzerland

Location

Klinik für Hämatologie und Onkologie Hirslanden Zürich AG

Zurich, 8032, Switzerland

Location

Onkozentrum Klinik im Park

Zurich, 8038, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

Stadtspital Zürich Triemli

Zurich, CH-8063, Switzerland

Location

Related Publications (1)

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roger von Moos, PD MD

  Kantonsspital Graubünden

  STUDY CHAIR

• Arnoud Templeton, MD

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Silke Gillessen, Prof

  Cantonal Hospital of St. Gallen

  STUDY CHAIR

• Andreas Müller, MD

  Kantonsspital Winterthur KSW

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2014
• First Posted: January 31, 2014
• Study Start: July 16, 2014
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

AU (2); CH (43); DE (5)