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

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ClinicalTrials.gov Identifier: NCT04447755
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : September 23, 2021
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Solid Tumors Drug: Lenvatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
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
Actual Study Start Date : July 30, 2020
Estimated Primary Completion Date : July 10, 2023
Estimated Study Completion Date : February 19, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Lenvatinib

Arm Intervention/treatment
Experimental: Lenvatinib
Participants receive lenvatinib 14 mg/m^2 once daily (QD) orally until progressive disease or unacceptable toxicity (up to approximately 1 year).
Drug: Lenvatinib
Lenvatinib capsules administered orally at 14 mg/m^2 QD
Other Names:
  • MK-7902
  • E7080
  • LENVIMA




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04447755


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Eisai Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04447755    
Other Study ID Numbers: 7902-013
2019-004441-33 ( EudraCT Number )
MK-7902-013 ( Other Identifier: Merck Protocol Number )
First Posted: June 25, 2020    Key Record Dates
Last Update Posted: September 23, 2021
Last Verified: September 2021
Individual Participant Data (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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action