Dose-escalation Study to Assess Safety, Tolerability and Pharmacokinetics of MEDI-573 in Japanese Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cancer, Advanced Solid Malignancies

Intervention / Treatment
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* Drug: MEDI-573


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI-573<br>MEDI-573 | Drug: MEDI-573<br>* MEDI-573 will be administrated once 7 days in Cohort 1 and 2, and once every 21 days in Cohort 3 as a IV infusion as part of a 21-day treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (based on CTCAE version 4.0), laboratory values, vital sign measurements, ECG, Physical Examination | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | All AEs will be collected throughout the study, from informed consent until 30 days after the end of study treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of MEDI-573 (by measuring anti-MEDI-573 antibodies) | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | 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 | 
| Anti-tumor activity of MEDI-573 using Response Evaluation Criteria in Solid Tumors(RECIST) | subjects who discontinue the study treatment for reasons other than disease progression or initiation of alternative anticancer therapy will undergo tumor assessment 3 months after the last dose of MEDI-573). The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | Tumor assessment by RECIST 1.1 every 2 cycles | 
| Pharmacokinetics, - Cmax | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3:Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 
| Pharmacokinetics,- Cmax at steady state (Cmax, ss) | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 
| Pharmacokinetics - time to maximum concentration (tmax) | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 
| Pharmacokinetics, - terminal elimination rate constant (λz) | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 
| Pharmacokinetics - (AUC(0-t)) | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 
| Pharmacokinetics - total clearance and terminal phase (Vz) of MEDI-573 | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 
| Pharmacodynamics: - Insulin-like growth factor (IGF)-I and IGF-II on circulating plasma levels of MEDI-573 | The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive. | For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, cancer, solid tumours, advanced solid malignancies, dose escalation, Insulin like growth factor, Japanese