Clinical Trials /

Phase I/II Study of Avelumab in Pediatric Cancer Subjects

NCT03451825

Description:

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.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study of Avelumab in Pediatric Cancer Subjects
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MS100070-0306
  • SECONDARY ID: 2017-002985-28
  • NCT ID: NCT03451825

Conditions

  • Refractory or Relapsed Solid Tumors
  • Lymphoma

Interventions

DrugSynonymsArms
AvelumabPhase 1: Avelumab
AvelumabPhase 2, Cohort 1: Avelumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1: AvelumabExperimental
  • Avelumab
Phase 2, Cohort 1: AvelumabExperimental
  • Avelumab
Phase 2, Cohort 2: AvelumabExperimental
  • Avelumab

Eligibility Criteria

        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
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Overall Survival (OS) Time
Time Frame:Time from first dose until death, assessed up to maximum of 48 months
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Maximum Observed Plasma Concentration (Cmax) of Single and Multiple Dose of Avelumab
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Half life (t1/2) of Single and Multiple Dose of Avelumab
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Minimum Post-dose Trough Concentration of Single and Multiple Dose of Avelumab
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Tumor-Infiltrating T-cell Levels
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: T-cell Population in Blood
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Number of T-cell, B-cell and NK-cell in Blood
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Vaccination-Related Antibody Concentrations
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Body Temperature
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Heart Rate
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Respiratory Rate
Time Frame:Baseline up to 48 months
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Systolic and Diastolic Blood Pressure
Time Frame:Baseline up to 48 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • Avelumab
  • Anti PD-L1
  • Solid tumors
  • CNS tumors
  • Lymphoma
  • Pediatric subjects

Last Updated