A Study of Ramucirumab (LY3009806) in Children With Refractory Solid Tumors

July 23, 2021 updated by: Eli Lilly and Company

A Phase 1 Study Of Ramucirumab, a Human Monoclonal Antibody Against the Vascular Endothelial Growth Factor-2 (VEGFR-2) Receptor in Children With Refractory Solid Tumors, Including CNS Tumors

The main purpose of this study is to evaluate the safety of the study drug known as ramucirumab in children with recurrent or refractory solid tumors including central nervous system (CNS) tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

29

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

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Childrens Hospital of Alabama
    • California
      • Monrovia, California, United States, 91016
        • Children's Oncology Group
      • Orange, California, United States, 92868
        • Childrens Hospital of Orange County
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Children's Healthcare of Atlanta at Scottish Rite
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Mark O Harfield-Warren Grant Magnuson Clinical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health Systems
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University Medical School
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Children's Hospital Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • Childrens Hospital of Pittsburgh
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St Jude Childrens Research Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Childrens Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital Research Foundation
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

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

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Part A: participants with recurrent or refractory non-CNS solid tumors
  • Part B: participants with recurrent or refractory CNS tumors
  • Measurable or evaluable disease
  • No other therapeutic options
  • Performance Status: Karnofsky ≥50% for participants >16 years and Lansky ≥50 for participants ≤16 years

Exclusion Criteria:

  • Active or recent history of serious bleeding events
  • Active or recent history of gastrointestinal perforations, ulcers, fistulas or abscesses
  • Active or recent history of hypertensive crisis or hypertensive encephalopathy
  • Active non-healing wound or bone fracture
  • History of solid organ transplant

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ramucirumab

(Part A-Non-CNS Solid Tumors) Escalating doses of 8 milligrams per kilogram (mg/kg) or 12 mg/kg Ramucirumab administered as an intravenous infusion every 2 weeks (Q2W) with 3 doses per 42 day cycle.

(Part B-CNS Tumors) Participants received 12 mg/kg Ramucirumab as an intravenous injection Q2W with 3 doses per cycle.
Drug: Ramucirumab
Administered IV
Other Names:
  • LY3009806
  • IMC-1121B
  • Cyramza

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Number of Participants With Dose Limiting Toxicities (DLTs): Maximum Tolerated Dose of Ramucirumab
Time Frame: Baseline to Study Completion (Up to 42 Months)

A DLT is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0:

1. Any death not clearly due to the underlying disease or extraneous causes 2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity 3. Grade ≥4 neutropenia or thrombocytopenia >7 days 4. Grade ≥3 thrombocytopenia with bleeding 5. Grade ≥3 nausea/vomiting or diarrhea>72 hours with adequate antiemetic and other supportive care 6. Grade ≥3 fatigue ≥1 week 7. Grade ≥3 electrolyte abnormality that lasts>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT.

8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
Baseline to Study Completion (Up to 42 Months)
Population Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
Time Frame: Predose, Cycle 1 Day 1 (end of infusion (EOI), 1 hour after EOI) and Cycle 1 Day 43 (1 hour after EOI)
Population Pharmacokinetics (PK): Minimum observed plasma concentration of Ramucirumab.
Predose, Cycle 1 Day 1 (end of infusion (EOI), 1 hour after EOI) and Cycle 1 Day 43 (1 hour after EOI)
Number of Participants With Anti-Ramucirumab Antibodies
Time Frame: Predose Cycle 1 Day 1 through Follow-Up (Up to 42 Months)
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
Predose Cycle 1 Day 1 through Follow-Up (Up to 42 Months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
Time Frame: Baseline to Date of Objective Disease Progression (Up to 42 Months)
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Baseline to Date of Objective Disease Progression (Up to 42 Months)
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)
Time Frame: Baseline to Date of Objective Disease Progression (Up to 42 Months)
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Baseline to Date of Objective Disease Progression (Up to 42 Months)
Duration of Response (DOR)
Time Frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 42 Months)
DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 42 Months)
Overall Survival
Time Frame: Baseline to Date of Death from Any Cause (Up to 42 Months)
Overall survival is defined as the time from date of randomization to the date of death (due to any cause). For participants whose last known status is alive at the data cutoff date for the analysis, time will be censored as the last contact date prior to the data cutoff date.
Baseline to Date of Death from Any Cause (Up to 42 Months)

Collaborators and Investigators

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

Sponsor

Eli Lilly and Company

Collaborators

Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 (Actual)

December 11, 2015

Primary Completion (Actual)

July 16, 2019

Study Completion (Actual)

July 16, 2019

Study Registration Dates

First Submitted

September 25, 2015

First Submitted That Met QC Criteria

September 29, 2015

First Posted (Estimate)

September 30, 2015

Study Record Updates

Last Update Posted (Actual)

August 17, 2021

Last Update Submitted That Met QC Criteria

July 23, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15542
  • I4T-MC-JVDA (Other Identifier: Eli Lilly and Company)
  • ADVL1416 (Other Identifier: Children's Oncology Group)

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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