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Phase I/II Study of Avelumab in Pediatric Cancer Subjects

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ClinicalTrials.gov Identifier: NCT03451825
Recruitment Status : Active, not recruiting
First Posted : March 2, 2018
Last Update Posted : June 15, 2021
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE February 26, 2018
First Posted Date  ICMJE March 2, 2018
Last Update Posted Date June 15, 2021
Actual Study Start Date  ICMJE March 7, 2018
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2018)
  • Phase 1: Occurrence and Severity of Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) [ Time Frame: From first dose of the study drug administration up to 30 days after the last dose (assessed up to maximum of 13 months) ]
  • Phase 1: Occurrence of Dose Limiting Toxicity [ Time Frame: Day 1 up to Day 28 ]
  • Phase 2: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator [ Time Frame: Time from first dose until confirmed disease progression assessed up to maximum of 48 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2018)
  • Phase 1: Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator [ Time Frame: Time from first dose until confirmed disease progression assessed up to maximum of 48 months ]
  • Phase 1 and Phase 2: Duration of Response (DOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator [ Time Frame: Time from first documented complete response (CR) or partial response (PR) to the date of first documentation of Progressive disease (PD) or death, assessed up to maximum of 48 months ]
  • Phase 1 and Phase 2: Time to Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator [ Time Frame: Time from first dose up to first documented CR or PR, assessed up to maximum of 48 months ]
  • Phase 1 and Phase 2: Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator [ Time Frame: Time from first dose up to the date of first documented disease progression or death due to any cause, assessed up to maximum of 48 months ]
  • Phase 1 and Phase 2: Overall Survival (OS) Time [ Time Frame: Time from first dose until death, assessed up to maximum of 48 months ]
  • Phase 1 and Phase 2: Occurrence and Severity of Treatment Emergent Adverse Events (TEAEs), AEs of Special Interest, and Treatment-Related AEs, According to the NCI-CTCAE Version 4.03 [ Time Frame: From first dose of the study drug administration up to 30 days after the last dose (assessed up to maximum of 48 months) ]
  • Phase 1 and Phase 2: Incidence of Laboratory Abnormalities as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Maximum Observed Plasma Concentration (Cmax) of Single and Multiple Dose of Avelumab [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Avelumab [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Half life (t1/2) of Single and Multiple Dose of Avelumab [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Minimum Post-dose Trough Concentration of Single and Multiple Dose of Avelumab [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Immunogenicity as measured by Incidence of Antidrug Antibody (ADA) and Neutralizing Antibody (Nabs) [ Time Frame: Baseline up to 30 days after the last dose (assessed maximum up to 48 months) ]
  • Phase 1 and Phase 2: Tumor Programmed Death Ligand 1 (PD-L1) Expression Levels [ Time Frame: Baseline and at disease progression (assessed up to maximum of 48 months) ]
  • Phase 1 and Phase 2: Tumor-Infiltrating T-cell Levels [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: T-cell Population in Blood [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Number of T-cell, B-cell and NK-cell in Blood [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Vaccination-Related Antibody Concentrations [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Body Temperature [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Heart Rate [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Respiratory Rate [ Time Frame: Baseline up to 48 months ]
  • Phase 1 and Phase 2: Systolic and Diastolic Blood Pressure [ Time Frame: Baseline up to 48 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/II Study of Avelumab in Pediatric Cancer Subjects
Official Title  ICMJE Open-label, Phase I/II Study to Evaluate Pharmacokinetics, Pharmacodynamics, Safety, and Anticancer Activity of Avelumab in Pediatric Subjects From Birth to Less Than 18 Years of Age With Refractory or Relapsed Solid Tumors and Lymphoma
Brief Summary This is a multi-center, open-label, international study to evaluate the dose, safety and tolerability, antitumor activity, pharmacokinetic and pharmacodynamics of avelumab in pediatric subjects 0 to less than 18 years of age with refractory or relapsed malignant solid tumors (including central nervous system tumors) and lymphoma for which no standard therapy is available or for which the subject is not eligible for the existing therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Refractory or Relapsed Solid Tumors
  • Lymphoma
Intervention  ICMJE
  • Drug: Avelumab
    Subjects will receive avelumab administered intravenously (IV) once every 2 weeks.
  • Drug: Avelumab
    Subjects will receive avelumab at a recommended phase II dose (RP2D) adjudicated by a safety monitoring committee (SMC) from phase I part of the study.
Study Arms  ICMJE
  • Experimental: Phase 1: Avelumab
    Intervention: Drug: Avelumab
  • Experimental: Phase 2, Cohort 1: Avelumab
    Intervention: Drug: Avelumab
  • Experimental: Phase 2, Cohort 2: Avelumab
    Intervention: Drug: Avelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 22, 2020)
26
Original Estimated Enrollment  ICMJE
 (submitted: February 26, 2018)
148
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female subjects 0 to less than 18 years of age at the time of first treatment dose with histologically or cytologically confirmed solid malignant tumors (including CNS tumors) or lymphoma for which no standard therapy is available
  • Confirmed progression on or refractory to standard therapy or no standard therapy available.
  • Availability of archival formalin-fixed, paraffin-embedded block containing tumor tissue, or slides, or a fresh/recent tumor biopsy prior to avelumab treatment for subjects in Phase 2
  • Adequate bone marrow, kidney, and liver function
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
  • Concurrent anticancer treatment or immunosuppressive agents
  • Prior organ transplantation
  • Significant acute or chronic infections
  • Other significant diseases or conditions that might impair the subject's tolerance of trial treatment
  • Other protocol defined exclusion criteria could apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Denmark,   Korea, Republic of,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03451825
Other Study ID Numbers  ICMJE MS100070-0306
2017-002985-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP