Study of Avelumab in Combination With Lenvatinib for Children With Primary CNS Tumors
|
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: NCT05081180 |
|
Recruitment Status :
Recruiting
First Posted : October 18, 2021
Last Update Posted : June 7, 2023
|
Sponsor:
EMD Serono Research & Development Institute, Inc.
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 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
| 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. |
Primary Outcome Measures :
- 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 ]
- Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline (Day 1) up to Day 28 ]
- 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 :
- 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 ]
- 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 ]
- Dose Escalation Part 1: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters [ Time Frame: up to 876 days ]
- 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 ]
- 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 ]
- 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 ]
- Dose Escalation Part 1: Overall Survival (OS) [ Time Frame: up to 876 days ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Dose Escalation Part 1: Immunogenicity of Avelumab as Measured by Antidrug Antibody (ADA) Assay [ Time Frame: up to 876 days ]
- 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 ]
- 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 ]
- Dose Expansion Part 2: Number of Participants with Clinically Significant Changes in Laboratory Parameters [ Time Frame: up to Day 1534 ]
- 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 ]
- 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 ]
- Dose Expansion Part 2: Overall Survival (OS) [ Time Frame: up to Day 1534 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Dose Expansion Part 2: Immunogenicity of avelumab as measured by ADA assay [ Time Frame: up to Day 1534 ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| 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
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
| Contact: US Medical Information | 888-275-7376 | eMediUSA@emdserono.com | |
| Contact: Communication Center | +49 6151 72 5200 | service@emdgroup.com |
Locations
| 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
| Study Director: | Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany |
Additional Information:
| 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: | June 7, 2023 |
| Last Verified: | June 2023 |
| 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 |
| 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:
|
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 |