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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01577745
First received: April 5, 2012
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Biological: MEDI0639
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Determination of the MTD [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Anti-Tumor [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Assessments of antitumor activity will be based on the objective response rate, disease control rate, duration of response, progression-free survival, and overall survival.

  • Immunogenicity [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Immunogenicity The immunogenic potential of MEDI0639 will be assessed by summarizing the number and percentage of subjects who develop detectable antidrug antibody (ADA).


Estimated Enrollment: 33
Study Start Date: April 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI0639
Dose 1, Dose 2, Dose 3, Dose 4, Dose 5, Dose 6
Biological: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01577745

Locations
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06519
United States, Michigan
Research Site
Ann Arbor, Michigan, United States, 48109
United States, New York
Research Site
New York, New York, United States, 10016
United States, Texas
Research Site
Houston, Texas, United States, 77030
United States, Washington
Research Site
Seattle, Washington, United States, 98104
Sponsors and Collaborators
MedImmune LLC
Investigators
Principal Investigator: David Smith, MD University of Michigan
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01577745     History of Changes
Other Study ID Numbers: CD-ON-MEDI0639-1078
Study First Received: April 5, 2012
Last Updated: February 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Cancer

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 20, 2014