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

• ClinicalTrials.gov Identifier: NCT04447755
• Recruitment Status: Active, not recruiting
• First Posted: June 25, 2020
• Last Update Posted: October 13, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: June 23, 2020
• First Posted Date: June 25, 2020
• Last Update Posted Date: October 13, 2022
• Actual Study Start Date: July 30, 2020
• Actual Primary Completion Date: September 16, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 23, 2020)

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 [ Time Frame: Week 16 of treatment ]

ORR at Week 16 is 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 is 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 21, 2020)

• ORR per RECIST 1.1 or RANO Criteria (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  ORR is 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 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.
• Progression Free Survival (PFS) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  PFS is 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).
• Best Overall Response (BOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  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.
• Duration of Response (DOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  DOR 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 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.
• Disease Control Rate (DCR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  DCR is 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 is defined as disappearance of all target lesions, PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, and SD is 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 is 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.
• Clinical Benefit Rate (CBR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  CBR is 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 is defined as disappearance of all target lesions, PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD and SD is 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 is 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.
• Number of Participants who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 43 months ]
  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 percentage of participants who experience at least one AE will be reported.
• Number of Participants who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 43 months ]
  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 percentage of participants who discontinue study treatment due to an AE will be reported.
• Palatability Questionnaire Score For Lenvatinib Suspension Formulation [ Time Frame: Cycle 1 Day 1 (cycle = 28 days) ]
  A hedonic Visual Analog Scale (VAS) will be used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water. Palatability will be rated based on 5 categories: taste, appearance, smell, mouth feel, and overall acceptability. Participants will score each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). The VAS hedonic scale scores will be summarized using descriptive statistics for each cohort and the median score will be reported for each palatability category.
• Area Under the Concentration-Time Curve of lenvatinib From Time 0 to Infinity (AUC 0-inf) [ Time Frame: At designated time points on Cycle 1 Day 1 (post-dose), Cycle 1 Day 15 (pre-dose and post-dose), and Cycle 2 Day 1 (pre-dose and post-dose). A cycle is 28 days. ]
  Blood samples taken predose and at specified times postdose on Days 1-28 to determine the AUC 0-inf of Lenvatinib.

Original Secondary Outcome Measures (submitted: June 23, 2020)

• ORR per RECIST 1.1 or RANO Criteria (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  ORR is 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 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.
• Progression Free Survival (PFS) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  PFS is 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).
• Best Overall Response (BOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  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.
• Duration of Response (DOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  DOR 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 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.
• Disease Control Rate (DCR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  DCR is 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 is defined as disappearance of all target lesions, PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, and SD is 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 is 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.
• Clinical Benefit Rate (CBR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment [ Time Frame: Up to approximately 43 months ]
  CBR is 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 is defined as disappearance of all target lesions, PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD and SD is 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 is 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.
• Number of Participants who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 43 months ]
  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 percentage of participants who experience at least one AE will be reported.
• Number of Participants who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 43 months ]
  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 percentage of participants who discontinue study treatment due to an AE will be reported.
• Palatability Questionnaire Score For Lenvatinib Suspension Formulation [ Time Frame: Cycle 1 Day 1 (cycle = 28 days) ]
  A hedonic Visual Analog Scale (VAS) will be used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water. Palatability will be rated based on 5 categories: taste, appearance, smell, mouth feel, and overall acceptability. Participants will score each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). The VAS hedonic scale scores will be summarized using descriptive statistics for each cohort and the median score will be reported for each palatability category.
• Area Under the Concentration-Time Curve of lenvatinib From Time 0 to Infinity (AUC 0-inf) [ Time Frame: At designated time points on Cycle 1 Day 1 (post-dose), Cycle 1 Day 15 (pre-dose and post-dose), and Cycle 2 Day 1 (post-dose). A cycle is 28 days. ]
  Blood samples taken predose and at specified times postdose on Days 1-28 to determine the AUC 0-inf of Lenvatinib.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Lenvatinib (MK-7902) in Pediatric Participants With Relapsed or Refractory Solid Malignancies (MK-7902-013/E7080)
• Official Title: An Open-Label, Multicenter Phase 2 Basket Study to Evaluate the Antitumor Activity and Safety of Lenvatinib in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Malignancies
• Brief Summary: 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 will be enrolled into initial tumor-specific cohorts which will be expanded based on observed response.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Open Label

Primary Purpose: Treatment

• Condition: Relapsed or Refractory Solid Tumors

Intervention

Drug: Lenvatinib

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

Other Names:

• MK-7902
• E7080
• LENVIMA

Study Arms

Experimental: Lenvatinib

Participants receive lenvatinib 14 mg/m^2 once daily (QD) orally until progressive disease or unacceptable toxicity (up to approximately 1 year).

Intervention: Drug: Lenvatinib

• Publications *: Gaspar N, Campbell-Hewson Q, Gallego Melcon S, Locatelli F, Venkatramani R, Hecker-Nolting S, Gambart M, Bautista F, Thebaud E, Aerts I, Morland B, Rossig C, Canete Nieto A, Longhi A, Lervat C, Entz-Werle N, Strauss SJ, Marec-Berard P, Okpara CE, He C, Dutta L, Casanova M. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆. ESMO Open. 2021 Oct;6(5):100250. doi: 10.1016/j.esmoop.2021.100250. Epub 2021 Sep 22.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 10, 2022): 127
• Original Estimated Enrollment (submitted: June 23, 2020): 150
• Estimated Study Completion Date: February 19, 2024
• Actual Primary Completion Date: September 16, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Croatia, Czechia, France, Guatemala, Hungary, Israel, Italy, Korea, Republic of, New Zealand, Peru, Russian Federation, Serbia, South Africa, Spain, Sweden, Turkey, United States

Administrative Information

• NCT Number: NCT04447755
• Other Study ID Numbers: 7902-013; MK-7902-013 ( Other Identifier: Merck Protocol Number ); 2019-004441-33 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Eisai Inc.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: October 2022