Evaluation of Lenvatinib Efficacy and Safety in Pediatric Patients with Relapsed or Refractory High-Grade Glioma and Other Solid Tumors

Trial ID: 2024-512135-80-00
Protocol: MK-7902-013
Sponsor: Merck Sharp & Dohme LLC

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Diseases & Conditions

Rhabdomyosarcoma Neoplasm Primitive neuroectodermal tumour Glioma

Objectives

The primary objective of this study is to determine the **Objective Response Rate (ORR)** at Week 16 for each tumor type, using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or the Response Assessment in Neuro-Oncology (RANO) for High Grade Glioma (HGG) only, as assessed by the investigator. This is clinically relevant as it provides an early indication of the antitumor activity of **lenvatinib** in pediatric patients with relapsed or refractory solid malignancies, which can guide treatment decisions and further research.

Secondary objectives include:

Evaluating ORR by each tumor type per RECIST 1.1 or RANO (for HGG only) as assessed by the investigator.
Assessing Progression-free Survival (PFS) per RECIST 1.1 or RANO (for HGG only) by each tumor type.
Evaluating the Best Overall Response (BOR), Duration of Response (DOR), Disease Control Rate (DCR), and Clinical Benefit Rate (CBR) by each tumor type.
Evaluating the safety of lenvatinib (MK-7902).
Assessing the palatability and acceptability of the suspension formulation of lenvatinib.
Characterizing the pharmacokinetics (PK) of lenvatinib.

Participants

The clinical trial involves a total of **54 participants** who are between the ages of **2 and 21**. The study population includes both male and female subjects diagnosed with **High Grade Glioma (HGG)**, **Rhabdomyosarcoma (RMS)**, **Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (pPNET)**, or other solid tumor types, excluding osteosarcoma. Participants were selected based on having histologically or cytologically documented relapsed or refractory pediatric solid malignancies. The trial population is characterized by a requirement for measurable disease as defined by specific response criteria and a performance status that meets established thresholds. Participants must demonstrate adequate organ function, including cardiac and neurologic function, and have controlled blood pressure. The study also considers lifestyle factors such as the use of approved contraception for male participants during the treatment period. The trial includes a vulnerable population, ensuring that all participants have fully recovered from prior anticancer therapy to a specified grade of adverse events, except for certain conditions like alopecia and ototoxicity.

Plans and Procedures

The clinical trial is designed as an open-label, multicenter Phase 2 study to evaluate the antitumor activity and safety of **lenvatinib** in pediatric patients with relapsed or refractory solid malignancies. The trial will involve children, adolescents, and young adults aged between 2 and 21 years who have been diagnosed with high-grade glioma, rhabdomyosarcoma, Ewing sarcoma, or other solid tumor types, excluding osteosarcoma. The primary objective is to determine the Objective Response Rate (ORR) at Week 16, assessed by the investigator using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for high-grade glioma. Secondary endpoints include progression-free survival, best overall response, duration of response, disease control rate, clinical benefit rate, and the number of participants experiencing adverse events.

The trial will commence with a screening visit to confirm eligibility based on inclusion criteria such as documented relapsed or refractory solid malignancy, measurable disease, adequate organ function, and controlled blood pressure. Participants will be administered **lenvatinib** in capsule form, with a maximum daily dose of 24 mg, for a treatment period of up to 42 days. The study will include regular follow-up visits to monitor the participants' response to treatment and any adverse events. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

Participants are expected to be involved in the study for the duration of the treatment period, with the possibility of early termination if they experience significant adverse events or if the investigator deems it necessary for safety reasons. The trial is estimated to conclude by February 19, 2025, with recruitment having started on May 25, 2021. The study is not categorized as low intervention and is conducted under the sponsorship of Merck & Co. Inc., with **lenvatinib** being the investigational product. The trial's design and procedures are structured to ensure rigorous assessment of the drug's efficacy and safety in the specified patient population.

Treatment

The clinical trial involves the administration of **Lenvatinib**, a chemical compound developed by Merck & Co. Inc. The pharmaceutical form of Lenvatinib is a capsule, identified by the sponsor product code MK-7902. The active substance, lenvatinib, is administered orally. The maximum daily dose is 24 mg, with a total maximum dose of 28,224 mg over a treatment period of 42 days. The trial does not involve a pediatric formulation, and the drug is not classified as an orphan drug. The capsules are intended for oral use, and the treatment regimen is designed to evaluate the antitumor activity and safety in children, adolescents, and young adults with relapsed or refractory solid malignancies.

In this study, Lenvatinib is the sole experimental medication, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial's primary objective is to determine the Objective Response Rate (ORR) at Week 16, assessed by the investigator using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for High Grade Glioma (HGG) only. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen.

Efficacy

The efficacy of the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)** at Week 16, evaluated by the investigator using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or the Response Assessment in Neuro-Oncology (RANO) criteria for High Grade Glioma (HGG). This primary endpoint will provide a measure of the antitumor activity of **Lenvatinib** in the study population, which includes children, adolescents, and young adults with relapsed or refractory solid malignancies.

Secondary endpoints will further evaluate efficacy and include the ORR per RECIST 1.1 or RANO criteria, Progression Free Survival (PFS), Best Overall Response (BOR), Duration of Response (DOR), Disease Control Rate (DCR), and Clinical Benefit Rate (CBR), all assessed by the investigator. Additionally, the trial will monitor the number of participants experiencing adverse events (AEs) and those discontinuing treatment due to AEs. A Palatability Questionnaire Score for the Lenvatinib suspension formulation and the Area Under the Concentration-Time Curve (AUC) of Lenvatinib from time 0 to infinity will also be evaluated.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Has histologically or cytologically documented relapsed, or refractory pediatric solid malignancy excluding osteosarcoma
Has measurable disease as defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for High Grade Glioma (HGG)
Has a performance status defined as follows: 1) Lansky Play Score ≥50 for participants up to and including 16 years of age 2) Karnofsky performance status (KPS) ≥50 for participants >16 years of age 3) Neurologic deficits in participants with primary central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment
Demonstrate adequate organ function
No clinical evidence of nephrotic syndrome.
Has adequate blood pressure (BP) control with or without antihypertensive medications
Has adequate cardiac function
Has adequate neurologic function
Participant must have fully recovered to Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) Grade ≤1 (except for alopecia, ototoxicity, and Grade ≤2 peripheral neuropathy) from the acute toxic effects of all prior anticancer therapy
Male participants must agree to use approved contraception during the treatment period and for at least 7 days after the last dose of study intervention and refrain from donating sperm during this period

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Exclusion Criteria

Has had major surgery within 3 weeks prior to Cycle 1 Day 1 (C1D1)
Has gastrointestinal (GI) bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 21 days prior to enrollment
Has CNS tumors with a history of symptomatic tumor hemorrhage
Has evidence of new intracranial hemorrhage of more than punctate size on MRI assessment obtained within 28 days prior to study enrollment
Has radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation
Has evidence of untreated CNS metastases (exception: participants with primary CNS tumors and leptomeningeal disease.
Has GI malabsorption, GI anastomosis, or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib
Has preexisting ≥Grade 3 GI or non-GI fistula
Has any active infection requiring systemic therapy
Known to be Human immunodeficiency virus (HIV) positive
Known active viral hepatitis (B or C) as demonstrated by positive serology. Testing for hepatitis B or hepatitis C is required at screening only when mandated by local health authority
Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has known hypersensitivity to any component of the investigational product (lenvatinib or ingredients)
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the stud
Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
Has non-healing wound, tumor ulceration, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrollment