Bone Metastasis
Conditions
Brief summary
This study evaluates MBC-11 (a conjugate of a bone-targeting vehicle (etidronate) and a cytostatic agent \[ara-C\] in patients with malignant tumors with CIBD. This is a first use in human.
Detailed description
A standard 3+3 dose escalation design to determine Maximum Tolerated Dose with consecutive different dose level cohort recruitment. The following dose levels to be investigated: 0.5 mg/kg, 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, 10 mg/kgm 20 mg/kg. The study for each patient consists of 14-days screening period, single dose administration of MBC-11 followed by 7-day safety monitoring and then 2 cycles of multiple use of MBC-11 (28 days each cycle, study drug is administered at Days1-5). In case of partial metabolic reaction/stable metabolic reaction therapy maybe prolonged up to 4 cycles (at investigator and sponsor consideration)
Interventions
DRUGMBC-11
0.5 mg/kg-10 mg/kg , IV (in the vein) on day 1-5 of each 28 day cycle. Number of cycles: 2, in case of partial metabolic reaction or stable metabolic reaction - up to 4.
Sponsors
Osteros Biomedica Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed malignant tumor (breast cancer, prostate cancer etc) * Bone metastases, documented by radiographs, bone scan * No available standard chemotherapy or no indication for chemotherapy at the time of screening * Eastern Cooperative Oncology Group \[ECOG\] status 0-2 * Adequate bone marrow function (hemoglobin ≥ 9 g/dL with or without transfusion requirement, absolute neutrophil count ≥ 1500/mm3, and platelets ≥ 75,000/mm3) * Adequate liver function (bilirubin ≤ 2 x Upper Limit of Normal \[ULN\], Alanine aminotransferase \[ALT\] ≤ 2.5 x ULN). * Adequate renal function (creatinine ≤ 1.5 x ULN) and creatinine clearance ≥ 50 mL/min \[measured or calculated by nomogram\]).
Exclusion criteria
* Systemic chemotherapy and/or investigational therapy within the previous 4 weeks * Fracture ≤ 6 month prior the inclusion in the study * Brain metastasis * Serum calcium levels \< 8.5 mg/dL (\< 2.2 mmol/L)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | up to 20 weeks | evaluation of adverse events, physical examination, laboratory parameters |
| Dose Limiting Toxicity [DLT] | up to 20 weeks | dose limiting toxicity is graded according to NCI CN CFT version 4 |
| Maximum tolerated dose | up to 20 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration [Cmax] of etidronate | 5 weeks | pharmacokinetics \[PK\] assessment of MBC-11 metabolite |
| Maximum Plasma Concentration [Cmax] of ara-U | 5 weeks | PK assessment of MBC-11 metabolite |
| Maximum Plasma Concentration [Cmax] of MBC-11 | 5 weeks | Cmax will be evaluated during Cycle 1 |
| Peak time [Tmax] for etidronate | 5 weeks | PK assessment of MBC-11metabolite |
| Peak time [Tmax] for MBC-11 | 5 weeks | PK parameters assessment of study drug |
| Pharmacodynamic parameters | up to 20 weeks | Levels of bone turnover markers is measured |
| Fluorodeoxyglucose positron emission tomography-computed tomography [FDG PET-CT] response after cycle 2 and cycle 4 therapy | up to 20 weeks | Response rate according to Positrone Emission Tomography Response Criteria in Solid Tumors \[PERCIST\] criteria using FDG PET/CT |
Outcome results
None listed