A Trial of MBC-11 in Patients With CIBD

Phase 1

Completed

• Conditions: Bone Metastasis
• Interventions: Drug: MBC-11

• Registration Number: NCT02673060
• Lead Sponsor: Osteros Biomedica Ltd

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)

Study Timeline

• Study Start: 2014-07
• Primary Completion: 2015-11
• Study Completion: 2015-12
• Study First Submitted: 2016-01-22
• Study First Submitted QC: 2016-02-01
• Study First Posted: 2016-02-03
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-28
• Last Update Posted: 2016-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
dose escalation of MBC-11	MBC-11	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Maximum Plasma Concentration [Cmax] of MBC-11	5 weeks	Cmax will be evaluated during Cycle 1
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
Peak time [Tmax] for MBC-11	5 weeks	PK parameters assessment of study drug
Peak time [Tmax] for etidronate	5 weeks	PK assessment of MBC-11metabolite
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
Pharmacodynamic parameters	up to 20 weeks	Levels of bone turnover markers is measured