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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 April 2024
• Main ID: NCT02051218
• Date of registration: 29/01/2014
• Prospective Registration: Yes
• Primary sponsor: Swiss Group for Clinical Cancer Research
• Public title: Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks
• Scientific title: Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks - A Non-Inferiority Phase III Trial
• Date of first enrolment: July 16, 2014
• Target sample size: 1380
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02051218
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Supportive Care. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Austria, Germany, Switzerland

Contacts

• Name: Silke Gillessen, Prof
• Affiliation: Cantonal Hospital of St. Gallen

• Name: Arnoud Templeton, MD
• Affiliation: Cantonal Hospital of St. Gallen

• Name: Roger von Moos, PD MD
• Affiliation: Kantonsspital Graubünden

• Name: Andreas Müller, MD
• Affiliation: Kantonsspital Winterthur KSW

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Prostate Cancer

Bone Metastases

Metastatic Breast Cancer

Intervention(s)

Drug: Denosumab (reduced dosing)

Drug: Denosumab (standard dosing)

Primary Outcome(s)

Time to first on-trial symptomatic skeletal event (SSE; Clinically significant pathological fracture, radiation therapy to bone, surgery to bone or spinal cord compression). [Time Frame: at the latest 5 years after randomization.]

Secondary Outcome(s)

Quality of Life measured by FACT-G and FACT-BP [Time Frame: at the latest 5 years after randomization.]

Health economic analysis [Time Frame: at the latest 5 years after randomization.]

Overall Survival (OS) [Time Frame: at the latest 5 years after randomization.]

Bone turnover markers [Time Frame: at the latest 5 years after randomization.]

Skeletal morbidity rate (SMR) [Time Frame: at the latest 5 years after randomization.]

Time to first and subsequent on-trial SSE [Time Frame: at the latest 5 years after randomization.]

Toxicity (focus on hypocalcaemia and osteonecrosis of the jaw) [Time Frame: at the latest 5 years after randomization.]

Skeletal morbidity period rate (SMPR) [Time Frame: at the latest 5 years after randomization.]

Secondary ID(s)

SAKK 96/12

000000685

2014-001189-87

Source(s) of Monetary Support

Please refer to primary and secondary sponsors