Studies objectives: To evaluate the safety, tolerability and efficacy of ACC given in combination with ZA or with Denosumab as compared to placebo given with ZA or with Denosumab as outline below: * Safety and Tolerability: * Adverse events (AEs) and serious AEs * Safety laboratory measurements * Hypercalcemic and hypercalciuric episodes * Treatment withdrawal due to AEs and overall Efficacy: * Skeletal Related Events (SREs) * Measurable and evaluable disease progression * Progression Free Survival (PFS) * Pain assessment via the VAS scale
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Subjects in this arm of the study will receive standard treatment with ZA or Denosumab (4 mg once every 4 weeks for ZA and 120mg (1.7ml injection) every 4 weeks for Denosumab) as well as AMOR-1 tablets, containing 200 mg elemental calcium per tablet, individually titrated up to the maximum level which does not induce grade 2 hypercalcemia.
microcrystalline cellulose
Soroka Medical Center
Beersheba, Israel
Changes in the number of Skeletal Related Events (SREs)
Time frame: Bone scan will take place at baseline and week 12
Time from randomization to onset of first SRE.
Time frame: Bone scan will be made on baseline and week 12
Proportion of subjects (%) with SREs.
Time frame: Bone scan will take place at baseline and week 12
Proportion of subjects (%) with evidence of measureable and evaluable disease progression or SREs.
Time frame: Bone scan will take place at baseline and week 12
Progression Free Survival (PFS).
Time frame: CT or MRI will be assessed on screening and week 12
Number of subjects that are receiving radiation as a rescue treatment
Time frame: An assessment will take place at week 2,4,6,8,10,12 16,20 and 24
Frequency and incidence of treatment emergent adverse events (TEAEs)
Time frame: Safety assessment will take place at week 2,4,6,8,10,12 16,20 and 24
Frequency and incidence of serious treatment emergent adverse events (TEAEs).
Time frame: Safety assessment will take place at weeks 2,4,6,8,10,12 16,20 and 24
Proportion of subjects (%) with hypercalcemic DLTs.
Time frame: Safety assessment will be made at weeks 2,4,6,8,10,12 16,20 and 24
Proportion of subjects (%) with any DLTs.
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Time frame: Safety assessment will take place at weeks 2,4,6,8,10,12 16,20 and 24
Number of hypercalciuric events.
Time frame: Urine calcium levels will be examined by urine tests, taking place at weeks 4,8,12,16,20 and 24