A Trial of MBC-11 in Patients With CIBD

Study Overview
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Brief Summary
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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
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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)

Official Title
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A Phase 1 Multicenter, Open-label, Dose-escalation Trial of MBC-11, an Etidronate-ara-C Conjugate in Patients With Malignant Tumors With Cancer-induced Bone Disease (CIBD)

Conditions
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Bone Metastasis

Intervention / Treatment
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* Drug: MBC-11


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose escalation of MBC-11<br>MBC-11 was administered in 5 consecutively recruited cohort in dose 0.5 mg/kg, 1 mg/kg, 2.5 mg/kg, 5 mg/kg,10 mg/kg accordingly. The dose escalation is aimed at determining the maximum tolerated dose (MTD) | Drug: MBC-11<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | evaluation of adverse events, physical examination, laboratory parameters | up to 20 weeks | 
| Dose Limiting Toxicity [DLT] | dose limiting toxicity is graded according to NCI CN CFT version 4 | up to 20 weeks | 
| Maximum tolerated dose |  | up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration [Cmax] of MBC-11 | Cmax will be evaluated during Cycle 1 | 5 weeks | 
| Pharmacodynamic parameters | Levels of bone turnover markers is measured | up to 20 weeks | 
| Fluorodeoxyglucose positron emission tomography-computed tomography [FDG PET-CT] response after cycle 2 and cycle 4 therapy | Response rate according to Positrone Emission Tomography Response Criteria in Solid Tumors [PERCIST] criteria using FDG PET/CT | up to 20 weeks | 
| Maximum Plasma Concentration [Cmax] of etidronate | pharmacokinetics [PK] assessment of MBC-11 metabolite | 5 weeks | 
| Maximum Plasma Concentration [Cmax] of ara-U | PK assessment of MBC-11 metabolite | 5 weeks | 
| Peak time [Tmax] for MBC-11 | PK parameters assessment of study drug | 5 weeks | 
| Peak time [Tmax] for etidronate | PK assessment of MBC-11metabolite | 5 weeks |