A Study of Lenvatinib (MK-7902) in Pediatric Participants With Relapsed or Refractory Solid Malignancies (MK-7902-013/E7080) (E7080-G000-231)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Relapsed or Refractory Solid Tumors

Treatments: Drug: Lenvatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04447755

HopSkip-013 (Other Identifier)

MK-7902-013 (Other Identifier)

U1111-1304-6856 (Registry Identifier)

7902-013

2019-004441-33 (EudraCT Number)

2024-512135-80-00 (Registry Identifier)

Details and patient eligibility

About

The main purpose of this study is to evaluate the antitumor activity and safety of lenvatinib (MK-7902/E7080) in children, adolescents, and young adults with relapsed or refractory solid malignancies after administration. Participants were enrolled into Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), high-grade glioma (HGG), diffuse midline glioma, medulloblastoma, ependymoma, and Other Solid Tumors Excluding Osteosarcoma, diffuse midline glioma, medulloblastoma, and ependymoma cohorts.

Enrollment: 127 patients

Sex: All

Ages: 2 to 21 years old

Volunteers: No Healthy Volunteers

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
• Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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127 participants in 7 patient groups

Ewing Sarcoma

Experimental group

Description:

Participants with Ewing sarcoma will receive lenvatinib 14 mg/m\^2 once daily (QD) orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib

Rhabdomyosarcoma

Experimental group

Description:

Participants with rhabdomyosarcoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib

High Grade Glioma

Experimental group

Description:

Participants with high grade glioma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib

Diffuse Midline Glioma

Experimental group

Description:

Participants with diffuse midline glioma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib

Medulloblastoma

Experimental group

Description:

Participants with medulloblastoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib

Ependymoma

Experimental group

Description:

Participants with ependymoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib

Other Solid Tumors Excluding Osteosarcoma, Diffuse Midline Glioma, Medulloblastoma and Ependymoma

Experimental group

Description:

Participants with other solid tumors will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Treatment:

Drug: Lenvatinib