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Trial record 1 of 1 for:    ADVL1416
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A Study of Ramucirumab (LY3009806) in Children With Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT02564198
Recruitment Status : Completed
First Posted : September 30, 2015
Results First Posted : August 17, 2021
Last Update Posted : August 17, 2021
Sponsor:
Collaborator:
Children's Oncology Group
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Pediatric Solid Tumor Refractory Tumor Recurrent Tumor CNS Malignancies Drug: Ramucirumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 11, 2015
Actual Primary Completion Date : July 16, 2019
Actual Study Completion Date : July 16, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ramucirumab

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




Primary Outcome Measures :
  1. 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.


  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02564198


Locations
Show Show 21 study locations
Sponsors and Collaborators
Eli Lilly and Company
Children's Oncology Group
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] January 31, 2019
Statistical Analysis Plan  [PDF] January 21, 2019

Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02564198    
Other Study ID Numbers: 15542
I4T-MC-JVDA ( Other Identifier: Eli Lilly and Company )
ADVL1416 ( Other Identifier: Children's Oncology Group )
First Posted: September 30, 2015    Key Record Dates
Results First Posted: August 17, 2021
Last Update Posted: August 17, 2021
Last Verified: July 2021
Keywords provided by Eli Lilly and Company:
relapsed pediatric solid tumors
unspecified childhood solid tumor
brain and central nervous system tumors
Additional relevant MeSH terms:
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Neoplasms
Recurrence
Disease Attributes
Pathologic Processes
Ramucirumab
Antineoplastic Agents