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.
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
Drug | Synonyms | Arms |
---|
Avelumab | | Phase 1: Avelumab |
Avelumab | | Phase 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
Name | Type | Description | Interventions |
---|
Phase 1: Avelumab | Experimental | | |
Phase 2, Cohort 1: Avelumab | Experimental | | |
Phase 2, Cohort 2: Avelumab | Experimental | | |
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: | Active, not recruiting |
Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- Avelumab
- Anti PD-L1
- Solid tumors
- CNS tumors
- Lymphoma
- Pediatric subjects
Last Updated
June 15, 2021