Back to resultsA Trial of MBC-11 in Patients With CIBD
Primary Purpose
Bone Metastasis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MBC-11
Sponsored by
About this trial
This is an interventional treatment trial for Bone Metastasis
Eligibility Criteria
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)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
dose escalation of MBC-11
Arm Description
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)
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
evaluation of adverse events, physical examination, laboratory parameters
Dose Limiting Toxicity [DLT]
dose limiting toxicity is graded according to NCI CN CFT version 4
Maximum tolerated dose
Secondary Outcome Measures
Maximum Plasma Concentration [Cmax] of MBC-11
Cmax will be evaluated during Cycle 1
Pharmacodynamic parameters
Levels of bone turnover markers is measured
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
Maximum Plasma Concentration [Cmax] of etidronate
pharmacokinetics [PK] assessment of MBC-11 metabolite
Maximum Plasma Concentration [Cmax] of ara-U
PK assessment of MBC-11 metabolite
Peak time [Tmax] for MBC-11
PK parameters assessment of study drug
Peak time [Tmax] for etidronate
PK assessment of MBC-11metabolite
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02673060
Brief Title
A Trial of MBC-11 in Patients With CIBD
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Osteros Biomedica Ltd
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Metastasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
dose escalation of MBC-11
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
MBC-11
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
evaluation of adverse events, physical examination, laboratory parameters
Time Frame
up to 20 weeks
Title
Dose Limiting Toxicity [DLT]
Description
dose limiting toxicity is graded according to NCI CN CFT version 4
Time Frame
up to 20 weeks
Title
Maximum tolerated dose
Time Frame
up to 20 weeks
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration [Cmax] of MBC-11
Description
Cmax will be evaluated during Cycle 1
Time Frame
5 weeks
Title
Pharmacodynamic parameters
Description
Levels of bone turnover markers is measured
Time Frame
up to 20 weeks
Title
Fluorodeoxyglucose positron emission tomography-computed tomography [FDG PET-CT] response after cycle 2 and cycle 4 therapy
Description
Response rate according to Positrone Emission Tomography Response Criteria in Solid Tumors [PERCIST] criteria using FDG PET/CT
Time Frame
up to 20 weeks
Title
Maximum Plasma Concentration [Cmax] of etidronate
Description
pharmacokinetics [PK] assessment of MBC-11 metabolite
Time Frame
5 weeks
Title
Maximum Plasma Concentration [Cmax] of ara-U
Description
PK assessment of MBC-11 metabolite
Time Frame
5 weeks
Title
Peak time [Tmax] for MBC-11
Description
PK parameters assessment of study drug
Time Frame
5 weeks
Title
Peak time [Tmax] for etidronate
Description
PK assessment of MBC-11metabolite
Time Frame
5 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30413669
Citation
Zinnen SP, Karpeisky A, Von Hoff DD, Plekhova L, Alexandrov A. First-in-Human Phase I Study of MBC-11, a Novel Bone-Targeted Cytarabine-Etidronate Conjugate in Patients with Cancer-Induced Bone Disease. Oncologist. 2019 Mar;24(3):303-e102. doi: 10.1634/theoncologist.2018-0707. Epub 2018 Nov 9.
Results Reference
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A Trial of MBC-11 in Patients With CIBD
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