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

Eli Lilly and Company29 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pediatric Solid Tumor Refractory Tumor Recurrent Tumor CNS Malignancies

Interventions

RamucirumabDRUG

Administered IV

Eligibility

Sex: ALLMin age: 12 MonthsMax age: 21 Years

Medical Language ↔ Plain English

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

Locations (21)

Childrens Hospital of Alabama

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline to Study Completion (Up to 42 Months)

Population Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Population Pharmacokinetics (PK): Minimum observed plasma concentration 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)

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.

Time frame: Predose Cycle 1 Day 1 through Follow-Up (Up to 42 Months)

Secondary Outcomes

Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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.

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.

Time frame: Baseline to Date of Objective Disease Progression (Up to 42 Months)

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.

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)