Clinical trial NCT01340040: Dose-escalation Study to Assess Safety, Tolerability and Pharmacokinetics of MEDI-573 in Japanese Subjects
Official title: A Phase 1, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI-573, a Fully Human Monoclonal Antibody Directed Against Insulin-like Growth Factors I and II, in Japanese Subjects With Advanced Solid Tumours Refractory to Standard Therapy or for Which No Standard Therapy Exists
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Advanced Solid Malignancies
Keywords: Phase I
cancer
solid tumours
advanced solid malignancies
dose escalation
Insulin like growth factor
Japanese
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: MedImmune LLC
First posted: 2011-04-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to explore the safety and tolerability of MEDI-573 in Japanese subjects with advanced solid tumours refractory to standard therapy or for which no standard therapy exists.


Eligibility criteria: Inclusion Criteria:

* Japanese men or women at least 20 years of age
* Histological or cytological confirmation of a solid, malignant tumour excluding lymphoma that is refractory to standard therapies or for which no standard therapies exist
* WHO performance status 0-2 with no deterioration over the previous 2 weeks

Exclusion Criteria:

* Previous therapy with medication against IGF (ie, monoclonal antibodies with IGF-1R or IGF-targeting tyrosine kinase inhibitors)
* Inadequate bone marrow reserve or organ function
* Poorly controlled diabetes mellitus as defined by the investigator's assessment and/or glycosylated hemoglobin (HbA1c) reading \> 6.5% within 28 days prior to the first dose of MEDI-573
* History of allergy or reaction to any component of the MEDI-573 formulation or drugs with a similar chemical structure or class to MEDI-573

Primary outcomes:
measure: Number of participants with adverse events (based on CTCAE version 4.0), laboratory values, vital sign measurements, ECG, Physical Examination
timeFrame: All AEs will be collected throughout the study, from informed consent until 30 days after the end of study treatment.
Secondary outcomes:
measure: Immunogenicity of MEDI-573 (by measuring anti-MEDI-573 antibodies)
timeFrame: For Cohorts 1, 2 and 3:day 1 (pre-dose) of every cycle; 30 days after the last dose; 3 months after the last dose
measure: Anti-tumor activity of MEDI-573 using Response Evaluation Criteria in Solid Tumors(RECIST)
timeFrame: Tumor assessment by RECIST 1.1 every 2 cycles
measure: Pharmacokinetics, - Cmax
timeFrame: For Cohorts 1, 2 and 3:Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
measure: Pharmacokinetics,- Cmax at steady state (Cmax, ss)
timeFrame: For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
measure: Pharmacokinetics - time to maximum concentration (tmax)
timeFrame: For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
measure: Pharmacokinetics, - terminal elimination rate constant (λz)
timeFrame: For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
measure: Pharmacokinetics - (AUC(0-t))
timeFrame: For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
measure: Pharmacokinetics - total clearance and terminal phase (Vz) of MEDI-573
timeFrame: For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
measure: Pharmacodynamics: - Insulin-like growth factor (IGF)-I and IGF-II on circulating plasma levels of MEDI-573
timeFrame: For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.
Other outcomes:
Locations:
city: Matsuyama
country: Japan
facility: Research Site
state: Ehime
Study officials:
affiliation: MedImmune LLC
name: Edward Bradley, MD
role: STUDY_DIRECTOR
References:
citation: Iguchi H, Nishina T, Nogami N, Kozuki T, Yamagiwa Y, Yagawa K. Phase I dose-escalation study evaluating safety, tolerability and pharmacokinetics of MEDI-573, a dual IGF-I/II neutralizing antibody, in Japanese patients with advanced solid tumours. Invest New Drugs. 2015 Feb;33(1):194-200. doi: 10.1007/s10637-014-0170-x. Epub 2014 Oct 25.