Clinical Trials /

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

NCT04447755

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 7902-013
  • SECONDARY ID: 2019-004441-33
  • SECONDARY ID: MK-7902-013
  • NCT ID: NCT04447755

Conditions

  • Relapsed or Refractory Solid Tumors

Interventions

DrugSynonymsArms
LenvatinibMK-7902, E7080, LENVIMALenvatinib

Purpose

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.

Trial Arms

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

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 30 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:

          -  Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first
             dose of study intervention

          -  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

          -  A clinically significant ECG abnormality, including a marked baseline prolonged QT or
             QT interval corrected for heart rate (QTc) interval (eg, a repeated demonstration of a
             QTc interval >480 msec)

          -  Known to be Human immunodeficiency virus (HIV) positive

          -  Active viral hepatitis (B or C) as demonstrated by positive serology

          -  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 study
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:ORR per RECIST 1.1 or RANO Criteria (for HGG only), by Investigator Assessment
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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).
Measure:Best Overall Response (BOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Clinical Benefit Rate (CBR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Number of Participants who Experience an Adverse Event (AE)
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Number of Participants who Discontinue Study Treatment Due to an AE
Time Frame:Up to approximately 43 months
Safety Issue:
Description: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.
Measure:Palatability Questionnaire Score For Lenvatinib Suspension Formulation
Time Frame:Cycle 1 Day 1 (cycle = 28 days)
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description:Blood samples taken predose and at specified times postdose on Days 1-28 to determine the AUC 0-inf of Lenvatinib.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Last Updated

July 29, 2020