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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01577745
• Other study ID #: CD-ON-MEDI0639-1078
• Status: Completed
• Phase: Phase 1
• First received: April 5, 2012
• Last updated: April 27, 2016
• Start date: April 2012
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK and immunogenicity of MEDI0639.

Description:

This is a first-time-in-human, Phase 1, multicenter, open-label, single-arm, dose-escalation (3+3) study to evaluate the safety, tolerability, antitumor activity, PK, and immunogenicity of MEDI0639 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exist. Up to 63 subjects will be enrolled at approximately 3 to 5 study centers in North America.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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:

• Hemoglobin = 10g/dL

• Absolute Neutrophil Count = 1500/mm3

• Platelet Count = 100,000/mm3

• AST & ALT = 2.5 x ULN

• Bilirubin = 1.5 x ULN

• 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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Biological:
• MEDI0639
MEDI0639 is an immunoglobulin G1 lambda (IgG1?) monoclonal antibody. MEDI0639 selectively binds to DLL4 and blocks its ability to bind to and activate signaling through the Notch receptors.

Locations

Country	Name	City	State
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Boston	Massachusetts
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	Seattle	Washington
United States	Research Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the MTD		12 months	No
Secondary	Anti-Tumor	Assessments of antitumor activity will be based on the objective response rate, disease control rate, duration of response, progression-free survival, and overall survival.	24 months	No
Secondary	Immunogenicity	Immunogenicity The immunogenic potential of MEDI0639 will be assessed by summarizing the number and percentage of subjects who develop detectable antidrug antibody (ADA).	24 months	No