Clinical trial NCT04447755: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed or Refractory Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2020-06-25
Enrollment: 127
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: ORR Per RECIST 1.1 or RANO Criteria (for HGG Only), by Investigator Assessment
timeFrame: Up to approximately 21 months
measure: Progression Free Survival (PFS) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment
timeFrame: Up to approximately 21 months
measure: Best Overall Response (BOR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment
timeFrame: Up to approximately 21 months
measure: Duration of Response (DOR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment
timeFrame: Up to approximately 21 months
measure: Disease Control Rate (DCR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment
timeFrame: Up to approximately 21 months
measure: Clinical Benefit Rate (CBR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment
timeFrame: Up to approximately 21 months
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 21 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 20 months
measure: Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Taste Category
timeFrame: Cycle 1 Day 1 (cycle = 28 days)
measure: Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Appearance Category
timeFrame: Cycle 1 Day 1 (cycle = 28 days)
measure: Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Smell Category
timeFrame: Cycle 1 Day 1 (cycle = 28 days)
measure: Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Mouth Feel Category
timeFrame: Cycle 1 Day 1 (cycle = 28 days)
measure: Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Overall Acceptability Category
timeFrame: Cycle 1 Day 1 (cycle = 28 days)
measure: Area Under the Concentration-Time Curve of Lenvatinib at Steady State (AUCss)
timeFrame: 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.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital of Colorado ( Site 0110)
state: Colorado
city: Cleveland
country: United States
facility: Cleveland Clinic ( Site 0119)
state: Ohio
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt ( Site 0102)
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center ( Site 0107)
state: Texas
city: Pilar
country: Argentina
facility: Hospital Universitario Austral ( Site 0126)
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital de Niños Ricardo Gutiérrez ( Site 0125)
state: Caba
city: Randwick
country: Australia
facility: Sydney Children's Hospital ( Site 0801)
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Children s Hospital ( Site 0804)
state: Queensland
city: Parkville
country: Australia
facility: Royal Childrens Hospital Melbourne ( Site 0802)
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children s Hospital ( Site 0803)
state: Western Australia
city: Gent
country: Belgium
facility: UZ Gent ( Site 0250)
state: Oost-Vlaanderen
city: Rijeka
country: Croatia
facility: Klinicki bolnicki centar Rijeka ( Site 0726)
state: Primorsko-goranska Zupanija
city: Zagreb
country: Croatia
facility: Klinika za djecje bolesti Zagreb ( Site 0725)
state: Zagrebacka Zupanija
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno Bohunice ( Site 0651)
state: Brno-mesto
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole ( Site 0650)
city: Lyon
country: France
facility: Centre Leon-Berard ( Site 0326)
state: Auvergne
city: Marseille
country: France
facility: Hopital La Timone ( Site 0328)
state: Bouches-du-Rhone
city: Villejuif
country: France
facility: Gustave Roussy ( Site 0327)
state: Val-de-Marne
city: Paris
country: France
facility: Institut Curie ( Site 0325)
city: Guatemala
country: Guatemala
facility: Unidad Nacional de Oncologia Pediatrica ( Site 0176)
city: Guatemala
country: Guatemala
facility: Medi-K Cayala ( Site 0177)
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0678)
state: Borsod-Abauj-Zemplen
city: Budapest
country: Hungary
facility: Semmelweis University ( Site 0675)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ( Site 0677)
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 0500)
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0410)
state: Roma
city: Firenze
country: Italy
facility: A.O.Universitaria Meyer-Oncology & Haematology Unit ( Site 0400)
state: Toscana
city: Genova
country: Italy
facility: Istituto Giannina Gaslini ( Site 0411)
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0401)
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita ( Site 0412)
city: Songpagu
country: Korea, Republic of
facility: Asan Medical Center ( Site 0876)
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0875)
city: Auckland
country: New Zealand
facility: Starship Childrens Hospital ( Site 0826)
city: San Isidro
country: Peru
facility: Clinica Anglo Americana ( Site 0203)
state: Lima
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev National Research Center ( Site 0550)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: St.Petersburg State Medical Univ. n.a. acad. I.P.Pavlov ( Site 0554)
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Research Center of specialized types medical care-Oncology ( Site 0553)
state: Sankt-Peterburg
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia ( Site 0780)
state: Beograd
city: Beograd
country: Serbia
facility: Univerzitetska decja klinika ( Site 0782)
city: Soweto
country: South Africa
facility: Wits Clinical Research ( Site 0579)
state: Gauteng
city: Cape Town
country: South Africa
facility: Cancercare Rondebosch Oncology ( Site 0575)
state: Western Cape
city: Parow
country: South Africa
facility: Tygerberg Hospital ( Site 0578)
state: Western Cape
city: Esplugues de Llobregat
country: Spain
facility: Hospital Universitario Sant Joan de Deu ( Site 0476)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Nino Jesus ( Site 0477)
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus Lund. ( Site 0525)
state: Skane Lan
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi ( Site 0603)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Onkoloji Enstitusu ( Site 0600)
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi ( Site 0601)
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi ( Site 0602)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.