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

Merck Sharp & Dohme LLC127 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

127

Conditions

Relapsed or Refractory Solid Tumors

Interventions

LenvatinibDRUG

Lenvatinib capsules administered orally at 14 mg/m\^2 QD

Eligibility

Sex: ALLMin age: 2 YearsMax age: 21 Years

Medical Language ↔ Plain English

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

Locations (49)

Outcomes

Primary Outcomes

Objective Response Rate (ORR) At Week 16 Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for High Grade Glioma [HGG] Only), by Investigator Assessment

ORR at Week 16 was defined as the percentage of participants with a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline SOD) as assessed by the investigator per RECIST 1.1 at 16 Weeks. For participants with HGG, response was assessed according to RANO criteria whereby overall response is based on both radiographic response (CR: disappearance of all target lesions, PR: sum of products of diameters \[SPD\] decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information.

Time frame: Up to 16 weeks

Secondary Outcomes

ORR Per RECIST 1.1 or RANO Criteria (for HGG Only), by Investigator Assessment

ORR was defined as the percentage of participants with a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) as assessed by the investigator per RECIST 1.1. For participants with HGG, response was assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information.

Time frame: Up to approximately 21 months

Progression Free Survival (PFS) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment

PFS was defined as the time from the date of the first administration of study drug until the date of first documentation of progressive disease (PD) per RECIST 1.1 or RANO (for HGG) or death (whichever occurs first).

Time frame: Up to approximately 21 months

Best Overall Response (BOR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment

Data from ClinicalTrials.gov

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Children's Hospital of Colorado ( Site 0110)

Aurora, Colorado, United States

Cleveland Clinic ( Site 0119)

Cleveland, Ohio, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt ( Site 0102)

Nashville, Tennessee, United States

Mary Crowley Cancer Research Center ( Site 0107)

Dallas, Texas, United States

Hospital Universitario Austral ( Site 0126)

Pilar, Buenos Aires, Argentina

Hospital de Niños Ricardo Gutiérrez ( Site 0125)

Buenos Aires, Buenos Aires F.D., Argentina

Sydney Children's Hospital ( Site 0801)

Randwick, New South Wales, Australia

Queensland Children s Hospital ( Site 0804)

Brisbane, Queensland, Australia

Royal Childrens Hospital Melbourne ( Site 0802)

Parkville, Victoria, Australia

Perth Children s Hospital ( Site 0803)

Nedlands, Western Australia, Australia

...and 39 more locations

BOR is defined as the participant's best confirmed response (CR or PR) over the treatment period as assessed by the investigator per RECIST 1.1 or RANO. As per RECIST 1.1, CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. For participants with HGG, response will be assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information.

Time frame: Up to approximately 21 months

Duration of Response (DOR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment

DOR was defined as the time from the date of the first documented CR or PR to the date first documentation of progressive disease or death (whichever occurs first). As per RECIST 1.1, CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. For participants with HGG, response will be assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information.

Time frame: Up to approximately 21 months

Disease Control Rate (DCR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment

DCR was defined as a BOR of CR or PR, or stable disease (SD). To be assigned a BOR of SD, the time from the first administration of study drug until the date of documented SD should be ≥7 weeks. As per RECIST 1.1, CR was defined as disappearance of all target lesions, PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For participants with HGG, response was assessed according to RANO criteria whereby overall response was based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value and SD: SPD \<50% decreased from baseline, but \<25% increased from nadir) and clinical performance status with steroid dose information.

Time frame: Up to approximately 21 months

Clinical Benefit Rate (CBR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment

CBR was defined as a BOR of CR or PR, or durable SD (Duration of SD should be ≥23 weeks since the first dose of the study treatment. As per RECIST 1.1, CR was defined as disappearance of all target lesions, PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For participants with HGG, response is assessed according to RANO criteria whereby overall response was based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value and SD: SPD \<50% decreased from baseline, but \<25% increased from nadir) and clinical performance status with steroid dose information.

Time frame: Up to approximately 21 months

Number of Participants Who Experienced an Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced at least one AE is reported.

Time frame: Up to approximately 50 months

Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to approximately 38 months

Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Taste Category

A hedonic Visual Analog Scale (VAS) was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the supplemental Statistical Analysis Plan (sSAP), all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the taste category is presented.

Time frame: Cycle 1 Day 1 (cycle = 28 days)

Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Appearance Category

A hedonic VAS was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the sSAP, all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the appearance category is presented.

Time frame: Cycle 1 Day 1 (cycle = 28 days)

Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Smell Category

Time frame: Cycle 1 Day 1 (cycle = 28 days)

Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Mouth Feel Category

Time frame: Cycle 1 Day 1 (cycle = 28 days)

Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Overall Acceptability Category

Time frame: Cycle 1 Day 1 (cycle = 28 days)

Area Under the Concentration-Time Curve of Lenvatinib at Steady State (AUCss)

Blood samples were taken predose and at specified times postdose on Days 1-28 to determine the AUCss of Lenvatinib.

Time frame: Cycle 1 Day 1 (0.5-4 and 6-10 hours post-dose), Cycle 1 Day 15 (pre-dose, 0.5-4, and 6-10 hours post-dose), and Cycle 2 Day 1 (pre-dose and 2-12 hours post-dose). A cycle is 28 days.