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Trial record 1 of 1 for:    NCT05081180
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Study of Avelumab in Combination With Lenvatinib for Children With Primary CNS Tumors

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ClinicalTrials.gov Identifier: NCT05081180
Recruitment Status : Recruiting
First Posted : October 18, 2021
Last Update Posted : March 12, 2024
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description
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Brief Summary:
This study consists of 2 parts: Dose Escalation Part 1 and Dose Expansion Part 2. The Dose Escalation Part 1 will evaluate the safety and tolerability of Avelumab in combination with Lenvatinib and determine the recommended Avelumab and Lenvatinib dose for expansion. Dose Expansion Part 2 will assess the efficacy of Avelumab in combination with Lenvatinib by Progression-free Survival in participants with pre-defined primary central nervous system (CNS) tumors.

Condition or disease Intervention/treatment Phase
Central Nervous System Tumors Drug: Avelumab Drug: Lenvatinib Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-arm, Multicenter Phase I/Ib Study of Avelumab + Lenvatinib in Children With Primary CNS Tumors
Actual Study Start Date : December 3, 2021
Estimated Primary Completion Date : December 21, 2025
Estimated Study Completion Date : December 21, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Avelumab + Lenvatinib Drug: Avelumab
Participants with primary CNS malignancies who have received at least 1 prior therapy will be enrolled into Dose Escalation Part 1 and will receive intravenous infusion at a flat dose or weight based dose of Avelumab, every 2 weeks (Q2W) until progression, unacceptable toxicity, or withdrawal of consent. Enrollment into part 1 of the study will end when Maximum tolerated dose (MTD) and/or a safe Recommended Dose for Expansion (RDE) for the expansion cohort is determined. Participants with defined CNS tumors will be enrolled into Dose Expansion Part 2 and will receive RDE in Part 2 until progression, unacceptable toxicity, or withdrawal of consent.

Drug: Lenvatinib
Participants with primary CNS malignancies who have received at least 1 prior therapy will be enrolled into Dose Escalation Part 1 and will receive daily oral escalated dose level of Lenvatinib until progression, unacceptable toxicity, or withdrawal of consent. Enrollment into part 1 of the study will end when MTD and/or a safe Recommended Dose for Expansion (RDE) for the expansion cohort is determined. Participants with defined CNS tumors will be enrolled into Dose Expansion Part 2 and will receive RDE of Lenvatinib in Part 2 until progression, unacceptable toxicity, or withdrawal of consent.


Outcome Measures
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Primary Outcome Measures :
  1. Dose Escalation Part 1: Number of Participants with Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater Than or Equal to (>=) 3 Treatment-emergent Adverse Event (TEAEs) According to National Cancer Institute-CTCAE Version 5.0 [ Time Frame: up to 857 days ]
  2. Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline (Day 1) up to Day 28 ]
  3. Dose Expansion Part 2: Progression-free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators [ Time Frame: until progressive disease or death, assessed up to Day 1534 ]

Secondary Outcome Measures :
  1. Dose Escalation Part 1: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs), Adverse Event of Special Interest (AESIs), AEs Leading to Deaths [ Time Frame: up to 876 days ]
  2. Dose Escalation Part 1: Number of Participants with Treatment-Emergent Adverse Events (AEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 [ Time Frame: up to 876 days ]
  3. Dose Escalation Part 1: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters [ Time Frame: up to 876 days ]
  4. Dose Escalation Part 1: Objective Response Rate (ORR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators [ Time Frame: up to 876 days ]
  5. Dose Escalation Part 1: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators [ Time Frame: up to 876 days ]
  6. Dose Escalation Part 1: Progression-Free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria [ Time Frame: until progressive disease or death, assessed up to 876 days ]
  7. Dose Escalation Part 1: Overall Survival (OS) [ Time Frame: up to 876 days ]
  8. Dose Escalation Part 1: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days ]
  9. Dose Escalation Part 1: Area Under the Serum Concentration-Time Curve From the Time of Dosing 336 Hours (AUC0-336 [hr]) of Avelumab [ Time Frame: Pre-dose up to 336 hours post-dose, assessed up to approximately 876 days ]
  10. Dose Escalation Part 1: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days ]
  11. Dose Escalation Part 1: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days ]
  12. Dose Escalation Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately 876 days ]
  13. Dose Escalation (Part 1): Area Under the Plasma Concentration-Time Curve From the Time of Dosing to 24 Hours (AUC0-24 [hr]) of Lenvatinib: [ Time Frame: Pre-dose up to 24 hours post-dose, assessed up to approximately 876 days ]
  14. Dose Escalation Part 1: Immunogenicity of Avelumab as Measured by Antidrug Antibody (ADA) Assay [ Time Frame: up to 876 days ]
  15. Dose Expansion Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs), Adverse Event of Special Interest (AESIs), AEs Leading to Deaths [ Time Frame: up to Day 1534 ]
  16. Dose Expansion Part 2: Number of Participants with Treatment-Emergent Adverse Events (AEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 [ Time Frame: up to Day 1534 ]
  17. Dose Expansion Part 2: Number of Participants with Clinically Significant Changes in Laboratory Parameters [ Time Frame: up to Day 1534 ]
  18. Dose Expansion Part 2: Objective Response Rate (ORR) Rate According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators [ Time Frame: up to Day 1534 ]
  19. Dose Expansion Part 2: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators [ Time Frame: up to Day 1534 ]
  20. Dose Expansion Part 2: Overall Survival (OS) [ Time Frame: up to Day 1534 ]
  21. Dose Expansion Part 2: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534 ]
  22. Dose Expansion Part 2:Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534 ]
  23. Dose Expansion Part 2: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534 ]
  24. Dose Expansion Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib [ Time Frame: Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534 ]
  25. Dose Expansion Part 2: Immunogenicity of avelumab as measured by ADA assay [ Time Frame: up to Day 1534 ]

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with histologically confirmed diagnosis of primary CNS malignancy as follows: a) Primary CNS tumors: the tumor should be considered high-grade histologically; prior radiotherapy is allowed; participants must have progressed after at least 1 prior systemic therapy, except for those with diffuse midline glioma with or without the H3 K27M mutation. b) Specific for participants with diffuse midline glioma with or without the H3 K27M mutation: prior radiotherapy is allowed; no more than 1 prior systemic therapy is allowed; participants with diffuse midline glioma with or without the H3 K27M mutation who have not received prior systemic therapy but have prior radiotherapy only are allowed to enroll
  • On screening scans, measurable disease by RANO criteria
  • Participants must have a Lansky performance status >= 50 for age <= 16 years or Karnofsky performance status >= 50 for age > 16 years at Screening
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Participants with low-grade gliomas, for example but not limited to, subependymal giant cell astrocytoma, pilocytic astrocytoma and World Health organization (WHO) Grade 1 tumors
  • Participants demonstrating evidence of worsening of neurologic deficit within 1 week prior to initiation of study interventions
  • Participants with bulky tumor, defined as: a) Tumor with any evidence of uncal herniation or midline shift; b) Tumor with a diameter of > 4 centimeters (cm) in 1 dimension on T2/ fluid-attenuated inversion recovery (FLAIR) images; c) Tumor that in the opinion of the Investigator shows significant mass effect
  • Participants are not eligible if they experience uncontrolled seizures, defined as: a) Seizures requiring regular use of rescue medications. b) Seizures requiring increasing doses of antiepileptic medications. c) Seizures that in the opinion of the Investigator compromise the ability of the participant to tolerate study intervention or interfere with study procedures
  • Participants who have received major surgery (including but not limited to neurosurgical resection, brain biopsy, or radiation to the primary brain tumor) within 28 days prior to the first dose of study interventions
  • Participants with history of intracranial hemorrhage/spinal cord hemorrhage within 28 days prior to the first dose of study interventions
  • Other protocol defined exclusion criteria could apply
Contacts and Locations
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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): NCT05081180


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

Locations
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United States, Missouri
Washington University Withdrawn
Saint Louis, Missouri, United States, 63110
Canada
CHU Sainte-Justine Recruiting
Montréal, Canada
Contact       s.perreault@umontreal.ca   
Principal Investigator: Sebastien Perreault         
The Hospital for Sick Children Recruiting
Toronto, Canada
Contact       eric.bouffet@sickkids.ca   
Principal Investigator: Eric Bouffet         
France
CHU Angers - Hôpital Hôtel Dieu - Service de Cancérologie Pédiatrique Recruiting
Angers Cedex 9, France
Contact       emdecarli@chu-angers.fr   
Principal Investigator: Emilie De Carli         
Hôpital de la Timone Recruiting
Marseille Cedex 05, France
Contact       nicolas.andre@mail.ap-hm.fr   
Principal Investigator: Nicolas André         
Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris Recruiting
Paris cedex 05, France
Contact       francois.doz@curie.fr   
Principal Investigator: François Doz         
Germany
Universitaetsklinikum Hamburg Eppendorf Recruiting
Hamburg, Germany
Contact       kordes@uke.de   
Principal Investigator: Uwe Kordes         
Universitaetsklinikum Muenster Recruiting
Muenster, Germany
Contact       kornelius.kerl@ukmuenster.de   
Principal Investigator: Kornelius Kerl         
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact       kanghj@snu.ac.kr   
Principal Investigator: Hyoung Jin Kang         
Severance Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of
Contact       jwhan@yuhs.ac   
Principal Investigator: Jung Woo Han         
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
More Information
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Additional Information:

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT05081180    
Other Study ID Numbers: MS100070_0087
2020-004397-22 ( EudraCT Number )
First Posted: October 18, 2021    Key Record Dates
Last Update Posted: March 12, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

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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
Lenvatinib
Tumors
Pediatric CNS tumors
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Lenvatinib
 Avelumab
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological