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Phase I/II Study of Avelumab in Pediatric Cancer Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03451825
Recruitment Status : Recruiting
First Posted : March 2, 2018
Last Update Posted : February 18, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

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.

Condition or disease Intervention/treatment Phase
Refractory or Relapsed Solid Tumors Lymphoma Drug: Avelumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : June 1, 2022
Estimated Study Completion Date : June 9, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Phase 1: Avelumab Drug: Avelumab
Subjects will receive avelumab administered intravenously (IV) once every 2 weeks.

Experimental: Phase 2, Cohort 1: Avelumab 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.

Experimental: Phase 2, Cohort 2: Avelumab 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.




Primary Outcome Measures :
  1. 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) ]
  2. Phase 1: Occurrence of Dose Limiting Toxicity [ Time Frame: Day 1 up to Day 28 ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Phase 1 and Phase 2: Overall Survival (OS) Time [ Time Frame: Time from first dose until death, assessed up to maximum of 48 months ]
  6. 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) ]
  7. 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 ]
  8. Phase 1 and Phase 2: Maximum Observed Plasma Concentration (Cmax) of Single and Multiple Dose of Avelumab [ Time Frame: Baseline up to 48 months ]
  9. 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 ]
  10. Phase 1 and Phase 2: Half life (t1/2) of Single and Multiple Dose of Avelumab [ Time Frame: Baseline up to 48 months ]
  11. Phase 1 and Phase 2: Minimum Post-dose Trough Concentration of Single and Multiple Dose of Avelumab [ Time Frame: Baseline up to 48 months ]
  12. 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) ]
  13. 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) ]
  14. Phase 1 and Phase 2: Tumor-Infiltrating T-cell Levels [ Time Frame: Baseline up to 48 months ]
  15. Phase 1 and Phase 2: T-cell Population in Blood [ Time Frame: Baseline up to 48 months ]
  16. Phase 1 and Phase 2: Number of T-cell, B-cell and NK-cell in Blood [ Time Frame: Baseline up to 48 months ]
  17. Phase 1 and Phase 2: Vaccination-Related Antibody Concentrations [ Time Frame: Baseline up to 48 months ]
  18. Phase 1 and Phase 2: Body Temperature [ Time Frame: Baseline up to 48 months ]
  19. Phase 1 and Phase 2: Heart Rate [ Time Frame: Baseline up to 48 months ]
  20. Phase 1 and Phase 2: Respiratory Rate [ Time Frame: Baseline up to 48 months ]
  21. Phase 1 and Phase 2: Systolic and Diastolic Blood Pressure [ Time Frame: Baseline up to 48 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03451825


Contacts
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Contact: US Medical Information 888-275-7376 service@emdgroup.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, New York
The Children's Hospital at Montefiore (CHAM) Recruiting
Bronx, New York, United States, 10467
Belgium
Cliniques Universitaires Saint-Luc Recruiting
Bruxelles, Belgium
UZ Leuven Recruiting
Leuven, Belgium
Canada
Children's Hospital - London Health Sciences Centre Recruiting
London, Canada
CHU Sainte-Justine Recruiting
Montréal, Canada
The Hospital for Sick Children Recruiting
Toronto, Canada
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Severance Hospital, Yonsei University Recruiting
Seoul, Korea, Republic of
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT03451825    
Other Study ID Numbers: MS100070-0306
2017-002985-28 ( EudraCT Number )
First Posted: March 2, 2018    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Avelumab
Anti PD-L1
Solid tumors
CNS tumors
Lymphoma
Pediatric subjects
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs