A Study of Lenvatinib (MK-7902) in Pediatric Participants With Relapsed or Refractory Solid Malignancies (MK-7902-013/E7080)
- Registration Number
- NCT04447755
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 127
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ewing Sarcoma Lenvatinib Participants with Ewing sarcoma will receive lenvatinib 14 mg/m\^2 once daily (QD) orally until progressive disease or unacceptable toxicity. Rhabdomyosarcoma Lenvatinib Participants with rhabdomyosarcoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity. Ependymoma Lenvatinib Participants with ependymoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity. Other Solid Tumors Excluding Osteosarcoma, Diffuse Midline Glioma, Medulloblastoma and Ependymoma Lenvatinib Participants with other solid tumors will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity. High Grade Glioma Lenvatinib Participants with high grade glioma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity. Medulloblastoma Lenvatinib Participants with medulloblastoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity. Diffuse Midline Glioma Lenvatinib Participants with diffuse midline glioma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method 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 Up to 16 weeks ORR at Week 16 was 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 was 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
Name Time Method Progression Free Survival (PFS) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment Up to approximately 21 months PFS was 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).
Disease Control Rate (DCR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment Up to approximately 21 months DCR was 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 was defined as disappearance of all target lesions, PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For participants with HGG, response was assessed according to RANO criteria whereby overall response was 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 Up to approximately 21 months CBR was 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 was defined as disappearance of all target lesions, PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD and SD was 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 was 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 Experienced an Adverse Event (AE) Up to approximately 21 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 number of participants who experienced at least one AE is reported.
Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Taste Category Cycle 1 Day 1 (cycle = 28 days) A hedonic Visual Analog Scale (VAS) was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the supplemental Statistical Analysis Plan (sSAP), all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the taste category is presented.
Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Smell Category Cycle 1 Day 1 (cycle = 28 days) A hedonic VAS was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the sSAP, all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the smell category is presented.
ORR Per RECIST 1.1 or RANO Criteria (for HGG Only), by Investigator Assessment Up to approximately 21 months ORR was 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 was 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.
Best Overall Response (BOR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment Up to approximately 21 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.
Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Appearance Category Cycle 1 Day 1 (cycle = 28 days) A hedonic VAS was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the sSAP, all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the appearance category is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to approximately 20 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 number of participants who discontinued study treatment due to an AE is reported.
Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Mouth Feel Category Cycle 1 Day 1 (cycle = 28 days) A hedonic VAS was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the sSAP, all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the mouth feel category is presented.
Duration of Response (DOR) Per RECIST 1.1 or RANO (for HGG Only), by Investigator Assessment Up to approximately 21 months DOR was 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 was defined as disappearance of all target lesions and PR was 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.
Palatability Questionnaire For Lenvatinib Suspension Formulation: Participant Responses by Overall Acceptability Category Cycle 1 Day 1 (cycle = 28 days) A hedonic VAS was used to assess taste likability or "palatability" of a lenvatinib suspension formulated with water or apple juice. Participants scored each category on a scale from 1-7 ranging from super bad (score = 1) to super good (score = 7). As pre-specified by the sSAP, all participants who received suspension formulation were evaluated for palatability and acceptability of the suspension formulation, and data were summarized in an overall safety analysis set irrespective of tumor type. The palatability score based on the overall acceptability category is presented.
Area Under the Concentration-Time Curve of Lenvatinib at Steady State (AUCss) 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. Blood samples were taken predose and at specified times postdose on Days 1-28 to determine the AUCss of Lenvatinib.
Trial Locations
- Locations (49)
Cancercare Rondebosch Oncology ( Site 0575)
🇿🇦Cape Town, Western Cape, South Africa
Monroe Carell Jr. Children's Hospital at Vanderbilt ( Site 0102)
🇺🇸Nashville, Tennessee, United States
UZ Gent ( Site 0250)
🇧🇪Gent, Oost-Vlaanderen, Belgium
Hospital de Niños Ricardo Gutiérrez ( Site 0125)
🇦🇷Ciudad Autonoma de Buenos Aires, Caba, Argentina
Institut Curie ( Site 0325)
🇫🇷Paris, France
Cleveland Clinic ( Site 0119)
🇺🇸Cleveland, Ohio, United States
IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0410)
🇮🇹Rome, Roma, Italy
Hacettepe Universitesi Tip Fakultesi ( Site 0603)
🇹🇷Ankara, Turkey
Debreceni Egyetem Klinikai Kozpont ( Site 0677)
🇭🇺Debrecen, Hungary
Asan Medical Center ( Site 0876)
🇰🇷Songpagu, Seoul, Korea, Republic of
Klinicki bolnicki centar Rijeka ( Site 0726)
🇭🇷Rijeka, Primorsko-goranska Zupanija, Croatia
Seoul National University Hospital ( Site 0875)
🇰🇷Seoul, Korea, Republic of
Perth Children s Hospital ( Site 0803)
🇦🇺Nedlands, Western Australia, Australia
Clinical Research Center of specialized types medical care-Oncology ( Site 0553)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Unidad Nacional de Oncologia Pediatrica ( Site 0176)
🇬🇹Guatemala, Guatemala
Tygerberg Hospital ( Site 0578)
🇿🇦Parow, Western Cape, South Africa
Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi ( Site 0602)
🇹🇷Izmir, Turkey
Semmelweis University ( Site 0675)
🇭🇺Budapest, Hungary
Chaim Sheba Medical Center ( Site 0500)
🇮🇱Ramat-Gan, Israel
Institute for Oncology and Radiology of Serbia ( Site 0780)
🇷🇸Belgrade, Beograd, Serbia
Fakultni nemocnice v Motole ( Site 0650)
🇨🇿Praha 5, Czechia
Istanbul Universitesi Onkoloji Enstitusu ( Site 0600)
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi ( Site 0601)
🇹🇷Izmir, Turkey
Children's Hospital of Colorado ( Site 0110)
🇺🇸Aurora, Colorado, United States
Ospedale Infantile Regina Margherita ( Site 0412)
🇮🇹Torino, Italy
Clinica Anglo Americana ( Site 0203)
🇵🇪San Isidro, Lima, Peru
Hospital Nino Jesus ( Site 0477)
🇪🇸Madrid, Spain
Medi-K Cayala ( Site 0177)
🇬🇹Guatemala, Guatemala
Skanes Universitetssjukhus Lund. ( Site 0525)
🇸🇪Lund, Skane Lan, Sweden
Istituto Giannina Gaslini ( Site 0411)
🇮🇹Genova, Italy
Klinika za djecje bolesti Zagreb ( Site 0725)
🇭🇷Zagreb, Zagrebacka Zupanija, Croatia
Hopital La Timone ( Site 0328)
🇫🇷Marseille, Bouches-du-Rhone, France
Gustave Roussy ( Site 0327)
🇫🇷Villejuif, Val-de-Marne, France
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 0678)
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0401)
🇮🇹Milano, Italy
A.O.Universitaria Meyer-Oncology & Haematology Unit ( Site 0400)
🇮🇹Firenze, Toscana, Italy
Dmitry Rogachev National Research Center ( Site 0550)
🇷🇺Moscow, Moskva, Russian Federation
Univerzitetska decja klinika ( Site 0782)
🇷🇸Beograd, Serbia
Mary Crowley Cancer Research Center ( Site 0107)
🇺🇸Dallas, Texas, United States
Sydney Children's Hospital ( Site 0801)
🇦🇺Randwick, New South Wales, Australia
Hospital Universitario Austral ( Site 0126)
🇦🇷Pilar, Buenos Aires, Argentina
Queensland Children s Hospital ( Site 0804)
🇦🇺Brisbane, Queensland, Australia
Starship Childrens Hospital ( Site 0826)
🇳🇿Auckland, New Zealand
Royal Childrens Hospital Melbourne ( Site 0802)
🇦🇺Parkville, Victoria, Australia
Fakultni Nemocnice Brno Bohunice ( Site 0651)
🇨🇿Brno, Brno-mesto, Czechia
Centre Leon-Berard ( Site 0326)
🇫🇷Lyon, Auvergne, France
St.Petersburg State Medical Univ. n.a. acad. I.P.Pavlov ( Site 0554)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Wits Clinical Research ( Site 0579)
🇿🇦Soweto, Gauteng, South Africa
Hospital Universitario Sant Joan de Deu ( Site 0476)
🇪🇸Esplugues de Llobregat, Barcelona, Spain