Description:
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.
Title
- Brief Title: A Study of Ramucirumab (LY3009806) in Children With Refractory Solid Tumors
- 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 IDs
- ORG STUDY ID:
15542
- SECONDARY ID:
I4T-MC-JVDA
- SECONDARY ID:
ADVL1416
- NCT ID:
NCT02564198
Conditions
- Pediatric Solid Tumor
- Refractory Tumor
- Recurrent Tumor
- CNS Malignancies
Interventions
| Drug | Synonyms | Arms |
|---|
| Ramucirumab | LY3009806, IMC-1121B, Cyramza | Ramucirumab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Ramucirumab | Experimental | (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. | |
Eligibility Criteria
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
| Maximum Eligible Age: | 21 Years |
| Minimum Eligible Age: | 12 Months |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival |
| Time Frame: | Baseline to Date of Death from Any Cause (Up to 42 Months) |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Eli Lilly and Company |
Trial Keywords
- relapsed pediatric solid tumors
- unspecified childhood solid tumor
- brain and central nervous system tumors
Last Updated
August 17, 2021
