We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04447755




Registration number
NCT04447755
Ethics application status
Date submitted
23/06/2020
Date registered
25/06/2020
Date last updated
29/04/2021

Titles & IDs
Public title
A Study of Lenvatinib (MK-7902) in Pediatric Participants With Relapsed or Refractory Solid Malignancies (MK-7902-013/E7080)
Scientific 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
Secondary ID [1] 0 0
2019-004441-33
Secondary ID [2] 0 0
7902-013
Universal Trial Number (UTN)
Trial acronym
E7080-G000-231
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lenvatinib

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


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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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 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.
Timepoint [1] 0 0
Week 16 of treatment
Secondary outcome [1] 0 0
ORR per RECIST 1.1 or RANO Criteria (for HGG only), by Investigator Assessment - 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.
Timepoint [1] 0 0
Up to approximately 43 months
Secondary outcome [2] 0 0
Progression Free Survival (PFS) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment - 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).
Timepoint [2] 0 0
Up to approximately 43 months
Secondary outcome [3] 0 0
Best Overall Response (BOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment - 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.
Timepoint [3] 0 0
Up to approximately 43 months
Secondary outcome [4] 0 0
Duration of Response (DOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment - 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.
Timepoint [4] 0 0
Up to approximately 43 months
Secondary outcome [5] 0 0
Disease Control Rate (DCR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment - 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.
Timepoint [5] 0 0
Up to approximately 43 months
Secondary outcome [6] 0 0
Clinical Benefit Rate (CBR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment - 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.
Timepoint [6] 0 0
Up to approximately 43 months
Secondary outcome [7] 0 0
Number of Participants who Experience 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 percentage of participants who experience at least one AE will be reported.
Timepoint [7] 0 0
Up to approximately 43 months
Secondary outcome [8] 0 0
Number of Participants who Discontinue Study Treatment Due to an 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 percentage of participants who discontinue study treatment due to an AE will be reported.
Timepoint [8] 0 0
Up to approximately 43 months
Secondary outcome [9] 0 0
Palatability Questionnaire Score For Lenvatinib Suspension Formulation - 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.
Timepoint [9] 0 0
Cycle 1 Day 1 (cycle = 28 days)
Secondary outcome [10] 0 0
Area Under the Concentration-Time Curve of lenvatinib From Time 0 to Infinity (AUC 0-inf) - Blood samples taken predose and at specified times postdose on Days 1-28 to determine the AUC 0-inf of Lenvatinib.
Timepoint [10] 0 0
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.

Eligibility
Key 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
Minimum age
2 Years
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital ( Site 0801) - Randwick
Recruitment hospital [2] 0 0
Queensland Children s Hospital ( Site 0804) - Brisbane
Recruitment hospital [3] 0 0
Perth Children s Hospital ( Site 0803) - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Caba
Country [7] 0 0
Croatia
State/province [7] 0 0
Primorsko-goranska Zupanija
Country [8] 0 0
Croatia
State/province [8] 0 0
Zagrebacka Zupanija
Country [9] 0 0
Czechia
State/province [9] 0 0
Brno-mesto
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 5
Country [11] 0 0
France
State/province [11] 0 0
Auvergne
Country [12] 0 0
France
State/province [12] 0 0
Bouches-du-Rhone
Country [13] 0 0
France
State/province [13] 0 0
Val-de-Marne
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Guatemala
State/province [15] 0 0
Guatemala
Country [16] 0 0
Hungary
State/province [16] 0 0
Borsod-Abauj-Zemplen
Country [17] 0 0
Hungary
State/province [17] 0 0
Budapest
Country [18] 0 0
Hungary
State/province [18] 0 0
Debrecen
Country [19] 0 0
Israel
State/province [19] 0 0
Tel Aviv
Country [20] 0 0
Italy
State/province [20] 0 0
Roma
Country [21] 0 0
Italy
State/province [21] 0 0
Toscana
Country [22] 0 0
Italy
State/province [22] 0 0
Torino
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
New Zealand
State/province [24] 0 0
Auckland
Country [25] 0 0
Peru
State/province [25] 0 0
Lima
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Moskva
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Sankt-Peterburg
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Sweden
State/province [30] 0 0
Skane Lan
Country [31] 0 0
Turkey
State/province [31] 0 0
Ankara
Country [32] 0 0
Turkey
State/province [32] 0 0
Istanbul
Country [33] 0 0
Turkey
State/province [33] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04447755
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04447755