Clinical trial NCT02673060: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bone Metastasis
Lead sponsor: Osteros Biomedica Ltd
Sponsor class: INDUSTRY
First posted: 2016-02-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

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)

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: up to 20 weeks
measure: Dose Limiting Toxicity [DLT]
timeFrame: up to 20 weeks
measure: Maximum tolerated dose
timeFrame: up to 20 weeks
Secondary outcomes:
measure: Maximum Plasma Concentration [Cmax] of MBC-11
timeFrame: 5 weeks
measure: Pharmacodynamic parameters
timeFrame: up to 20 weeks
measure: Fluorodeoxyglucose positron emission tomography-computed tomography [FDG PET-CT] response after cycle 2 and cycle 4 therapy
timeFrame: up to 20 weeks
measure: Maximum Plasma Concentration [Cmax] of etidronate
timeFrame: 5 weeks
measure: Maximum Plasma Concentration [Cmax] of ara-U
timeFrame: 5 weeks
measure: Peak time [Tmax] for MBC-11
timeFrame: 5 weeks
measure: Peak time [Tmax] for etidronate
timeFrame: 5 weeks
Other outcomes:
Locations:
Study officials:
References:
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.