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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01340040

Collaborator

MedImmune LLC (Industry)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Advanced Solid Malignancies	Drug: MEDI-573	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2011

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI-573 MEDI-573	Drug: MEDI-573 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.

Arm

Intervention/Treatment

Experimental: MEDI-573

MEDI-573

Drug: MEDI-573

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Immunogenicity of MEDI-573 (by measuring anti-MEDI-573 antibodies) [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]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Anti-tumor activity of MEDI-573 using Response Evaluation Criteria in Solid Tumors(RECIST) [Tumor assessment by RECIST 1.1 every 2 cycles]
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.
Pharmacokinetics, - Cmax [For Cohorts 1, 2 and 3:Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Pharmacokinetics,- Cmax at steady state (Cmax, ss) [For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Pharmacokinetics - time to maximum concentration (tmax) [For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Pharmacokinetics, - terminal elimination rate constant (λz) [For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Pharmacokinetics - (AUC(0-t)) [For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Pharmacokinetics - total clearance and terminal phase (Vz) of MEDI-573 [For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.
Pharmacodynamics: - Insulin-like growth factor (IGF)-I and IGF-II on circulating plasma levels of MEDI-573 [For Cohorts 1, 2 and 3: Multiple timepoints taken, begining at Day 1 and until 30 days after last dose.]
The total duration of this time frame can not be specified, as it depends on the number of treatments the subject may receive.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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