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

Pediatric Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02564198
• Other study ID #: 15542
• Secondary ID: I4T-MC-JVDAADVL1
• Status: Completed
• Phase: Phase 1
• Start date: December 11, 2015
• Est. completion date: July 16, 2019

Study information

• Verified date: July 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 16, 2019
• Est. primary completion date: July 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• CNS Malignancies
• Neoplasms
• Pediatric Solid Tumor
• Recurrent Tumor
• Refractory Tumor

Intervention

Drug:
• Ramucirumab
Administered IV

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Children's Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of Participants With Dose Limiting Toxicities (DLTs): Maximum Tolerated Dose of Ramucirumab	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)
Primary	Population Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab	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)
Primary	Number of Participants With Anti-Ramucirumab Antibodies	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	Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)	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)
Secondary	Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)	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)
Secondary	Duration of Response (DOR)	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)
Secondary	Overall Survival	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)

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