A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Advanced Solid Tumors

Study identifier:CD-ON-MEDI0639-1078

ClinicalTrials.gov identifier:NCT01577745

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI0639 in Adult Subjects with Advanced Solid Tumors

Medical condition

Solid Tumors

Phase

Phase 1

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 01 Apr 2012

Primary Completion Date: 01 Dec 2015

Study Completion Date: 01 Dec 2015

Study design

Allocation: N/A
Endpoint Classification: Safety
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2017 by MedImmune, LLC

Collaborators

None

Inclusion and exclusion criteria

Inclusion Criteria

- Histologically or cytologically confirmed solid tumors that are refractory to standard therapy or for which no standard therapy exist
- Age ≥ 18 years
- ECOG Performance Status of 0 or 1
- LVEF (measured by Echocardiogram) > 50%
- No gastrointestinal bleeding within 1 year of study entry.
- Adequate organ and marrow function:
o Hemoglobin ≥ 10g/dL
o Absolute Neutrophil Count ≥ 1500/mm3
o Platelet Count ≥ 100,000/mm3
o AST & ALT ≤ 2.5 x ULN
o Bilirubin ≤ 1.5 x ULN
o Cr Cl ≥ 50 mL/min (as determined by the Cockcroft-Gault equation or by 24-hour urine collection)
- Prior therapy against VEGF or VEGFRs including, but not limited to bevacizumab, sunitinib, sorafenib, pazopanib, motesanib (AMG706), or cediranib (AZD2171), is permitted so long as the agent does not have any known activity against DLL4 and the last dose received s at least 6 weeks prior to first dose of MEDI0639.
- Life expectancy ≥ 12 weeks
- Females of childbearing potential must be surgically sterile, have a sterile male partner, be premenarchal or at least 2 years postmenopausal, practice abstinence or otherwise must use 2 effective methods of contraception from the time of initiation of investigational product.
- Males, unless surgically sterile, must use 2 effective methods of contraception with a female partner and must agree to continue using such contraception for 90 days after the last dose of MEDI0639

Exclusion Criteria

- Concurrent enrollment in another investigational clinical study
- Receipt of any investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0639 or in the case of monoclonal antibodies, 6 weeks prior to the first dose of MEDI0639
- Concurrent or previous treatment with inhibitors of DLL4
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment
- Known bleeding diathesis, esophageal varices, or angioplasty
- Pulmonary hemorrhage or gross hemoptysis within 12 months
- Known arterial or venous thrombosis or pulmonary embolism within 2 years
- Concurrent use of systemic low molecular weight heparin or low dose warfarin
- Presence of brain metastases
- Cerebrovascular accident or transient ischemic attack within 2 years
- Cardiovascular events, such as myocardial infarction, unstable/severe angina, coronary/peripheral artery bypass graft, unstable cardiac arrhythmia requiring medication, congestive heart failure (NYHA > class II), within 2 years
- Tumors with squamous cell histology
- Major surgical procedure within 90 days
- Pregnancy or lactation
- Known HIV positive or Hepatitis A, B, or C infection

No locations available

Arms	Assigned Interventions
Experimental: MEDI0639 Cohort 1 Participants received MEDI0639 dose level 1 as a 60-minute intravenous (IV) infusion on Day 1 of each 21-day cycle.	Biological/Vaccine: MEDI0639 MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Experimental: MEDI0639 Cohort 2 Participants received MEDI0639 dose level 2 as a 60-minute IV infusion on Day 1 of each 21-day cycle.	Biological/Vaccine: MEDI0639 MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Experimental: MEDI0639 Cohort 3 Participants received MEDI0639 dose level 3 as a 60-minute IV infusion on Day 1 of each 21-day cycle.	Biological/Vaccine: MEDI0639 MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Experimental: MEDI0639 Cohort 4 Participants received MEDI0639 dose level 4 as a 60-minute IV infusion on Day 1 of each 21-day cycle.	Biological/Vaccine: MEDI0639 MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Experimental: MEDI0639 Cohort 5 Participants received MEDI0639 dose level 5 as a 60-minute IV infusion on Day 1 of each 21-day cycle.	Biological/Vaccine: MEDI0639 MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.
Experimental: MEDI0639 Cohort 6 Participants received MEDI0639 dose level 6 as a 60-minute IV infusion on Day 1 of each 21 day cycle.	Biological/Vaccine: MEDI0639 MEDI0639 is an immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]