A Trial of MBC-11 in Patients With CIBD

March 28, 2016 updated by: Osteros Biomedica Ltd

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: dose escalation of 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)
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration [Cmax] of MBC-11
Time Frame: 5 weeks
Cmax will be evaluated during Cycle 1
5 weeks
Pharmacodynamic parameters
Time Frame: up to 20 weeks
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
Time Frame: up to 20 weeks
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
Time Frame: 5 weeks
pharmacokinetics [PK] assessment of MBC-11 metabolite
5 weeks
Maximum Plasma Concentration [Cmax] of ara-U
Time Frame: 5 weeks
PK assessment of MBC-11 metabolite
5 weeks
Peak time [Tmax] for MBC-11
Time Frame: 5 weeks
PK parameters assessment of study drug
5 weeks
Peak time [Tmax] for etidronate
Time Frame: 5 weeks
PK assessment of MBC-11metabolite
5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

January 22, 2016

First Submitted That Met QC Criteria

February 1, 2016

First Posted (Estimate)

February 3, 2016

Study Record Updates

Last Update Posted (Estimate)

March 29, 2016

Last Update Submitted That Met QC Criteria

March 28, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • OB-MBC-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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