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

Phase 1

Completed

Conditions: Refractory Tumor
Pediatric Solid Tumor
Recurrent Tumor
CNS Malignancies

Interventions: Drug: Ramucirumab

Registration Number: NCT02564198

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ramucirumab	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Anti-Ramucirumab Antibodies	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.
Part A: Number of Participants With Dose Limiting Toxicities (DLTs): Maximum Tolerated Dose of Ramucirumab	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.
Population Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)	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.
Overall Survival	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.
Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)	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.
Duration of Response (DOR)	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.

Trial Locations

Locations (21): Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Texas Childrens Hospital
🇺🇸
Houston, Texas, United States
Seattle Children's Hospital Research Foundation
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Seattle, Washington, United States
Children's Hospital Medical Center
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Cincinnati, Ohio, United States
University of Michigan Health Systems
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Ann Arbor, Michigan, United States
Ann & Robert H Lurie Children's Hospital of Chicago
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Chicago, Illinois, United States
Medical College of Wisconsin
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Milwaukee, Wisconsin, United States
Children's Healthcare of Atlanta at Scottish Rite
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Atlanta, Georgia, United States
Childrens Hospital of Orange County
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Orange, California, United States
Children's National Medical Center
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Washington, District of Columbia, United States
Children's Oncology Group
🇺🇸
Monrovia, California, United States
Mark O Harfield-Warren Grant Magnuson Clinical Center
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Bethesda, Maryland, United States
Childrens Hospital of Pittsburgh
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Pittsburgh, Pennsylvania, United States
University of Minnesota Hospital
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Minneapolis, Minnesota, United States
Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, United States
Washington University Medical School
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Saint Louis, Missouri, United States
St Jude Childrens Research Hospital
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Memphis, Tennessee, United States
Childrens Hospital of Alabama
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Birmingham, Alabama, United States
University of California, San Francisco
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San Francisco, California, United States
Oregon Health and Science University
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Portland, Oregon, United States
Columbia University Medical Center
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New York, New York, United States