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JOURNAL ONKOLOGIE – STUDIE

Study of Avelumab in Combination With Lenvatinib for Children With Primary CNS Tumors

Rekrutierend

NCT-Nummer:
NCT05081180

Studienbeginn:
Dezember 2021

Letztes Update:
12.03.2024

Wirkstoff:
Avelumab, Lenvatinib

Indikation (Clinical Trials):
Nervous System Neoplasms, Central Nervous System Neoplasms

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 1

Sponsor:
EMD Serono Research & Development Institute, Inc.

Collaborator:
Merck KGaA, Darmstadt, Germany

Studienleiter

Medical Responsible
Study Director
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Kontakt

Studienlocations
(3 von 10)

Washington University
63110 Saint Louis
United StatesZurückgezogen» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

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:

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)

Geprüfte Regime

  • 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.
  • 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.

Quelle: ClinicalTrials.gov


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