Nesvacumab (REGN910/ SAR307746) and Aflibercept ("Ziv-aflibercept" in the U.S.) in Patients With Advanced Solid Malignancies

March 16, 2015 updated by: Regeneron Pharmaceuticals

A Phase 1b Study of Combined Angiogenesis Inhibition by Administering REGN910 and Aflibercept (Ziv-aflibercept) in Patients With Advanced Solid Malignancies

This is an open-label, multicenter, ascending, multiple dose study of nesvacumab (REGN910/ SAR307746) in combination with aflibercept ("ziv-aflibercept" in the U.S.)

Study Overview

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Toronto, Canada
    • Indiana
      • Indianapolis, Indiana, United States
    • New York
      • New York, New York, United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Texas
      • San Antonio, Texas, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion criteria include, but are not limited to, the following:

  1. Confirmed diagnosis of solid tumor malignancy
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  3. Adequate hepatic, renal and bone marrow function
  4. Resolution of toxicity from prior therapy (except alopecia) to grade less than or equal to 1

Exclusion Criteria:

Exclusion criteria include, but are not limited to, the following:

  1. Patients with brain metastases, spinal cord compression, carcinomatous meningitis, or other evidence of central nervous system involvement
  2. Either systolic BP greater than 140 mm Hg or diastolic BP greater than 90 mm Hg
  3. Patients with medical history of myocardial infarction, unstable angina pectoris, coronary/ peripheral artery bypass graft, congestive heart failure or ventricular arrhythmia
  4. Patients with deep vein thrombosis or pulmonary embolism within last 3 months
  5. Patients with serious non healing wound or acute ulcer
  6. Patients with treatment resistant or bleeding peptic ulcer disease, erosive esophagitis or gastritis, grade 3 or gastrointestinal bleeding/hemorrhage, infectious or inflammatory bowel disease, diverticulitis, or other uncontrolled thromboembolic event within last 3 months
  7. Patients with history of abdominal or tracheal-esophageal fistula
  8. Prior treatment with aflibercept (ziv-aflibercept), Ang2 or Tie2 inhibitors
  9. Prior treatment with bevacizumab within last 6 weeks
  10. Pregnant or breast-feeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Dose level 1
Dose level 2
Dose level 3
Dose level 1
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Dose level 2
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Experimental: Cohort 2
Dose level 1
Dose level 2
Dose level 3
Dose level 1
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Dose level 2
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Experimental: Cohort 4
Dose level 1
Dose level 2
Dose level 3
Dose level 1
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Dose level 2
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Experimental: Cohort 3a
Dose level 1
Dose level 2
Dose level 3
Dose level 1
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Dose level 2
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Experimental: Cohort 3b
Dose level 1
Dose level 2
Dose level 3
Dose level 1
Other Names:
  • In US: aflibercept is known as ziv-aflibercept
Dose level 2
Other Names:
  • In US: aflibercept is known as ziv-aflibercept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D)
Time Frame: Day 1 to Day 28
Determine the maximum tolerable dose or recommended phase 2 dose of nesvacumab (REGN910/ SAR307746) administered in combination with aflibercept (ziv-aflibercept) in patients with advanced solid malignancies
Day 1 to Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK)
Time Frame: Day 1 to Day 170
To assess PK parameters such as concentration of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept).
Day 1 to Day 170
Immunogenicity
Time Frame: Day 1 to Day 170
To assess the anti-drug antibodies of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept)
Day 1 to Day 170
Antitumor activity
Time Frame: Day 1 to Day 170
Objective tumor response according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1
Day 1 to Day 170
Pharmacodynamics (PD)
Time Frame: Day 1 to Day 170
Target inhibition biomarker changes, serum tumor markers
Day 1 to Day 170

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

September 17, 2012

First Submitted That Met QC Criteria

September 17, 2012

First Posted (Estimate)

September 20, 2012

Study Record Updates

Last Update Posted (Estimate)

March 17, 2015

Last Update Submitted That Met QC Criteria

March 16, 2015

Last Verified

March 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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