Summary
EudraCT Number:2021-003602-41
Sponsor's Protocol Code Number:2020-012-GLOB2
National Competent Authority:Spain - AEMPS
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-09-21
Trial results
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2021-003602-41
A.3Full title of the trial
AN OPEN-LABEL, MULTICENTER PHASE 1/2 STUDY OF SURUFATINIB IN COMBINATION WITH GEMCITABINE IN PEDIATRIC, ADOLESCENT, AND YOUNG ADULT PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS
ESTUDIO ABIERTO, MULTICÉNTRICO FASE 1/2 DE SURUFATINIB EN COMBINACIÓN CON GEMCITABINA EN PACIENTES PEDIÁTRICOS,
ADOLESCENTES Y ADULTOS JÓVENES CON TUMORES SÓLIDOS
RECURRENTES O REFRACTARIOS
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A Study of Surufatinib in Combination with Gemcitabine in Pediatric, Adolescent, and Young Adult Patients with Recurrent or Refractory Solid Tumors
Estudio ade surufatinib en combinación con gemcitabina en pacientes pediátricos, adolescentes y adultos jóvenes con tumores sólidos recurrentes o refractarios.
A.4.1Sponsor's protocol code number2020-012-GLOB2
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05093322
A.7Trial is part of a Paediatric Investigation Plan Yes
A.8EMA Decision number of Paediatric Investigation PlanP/142/2021
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorHUTCHMED Limited
B.1.3.4CountryChina
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportHUTCHMED Limited
B.4.2CountryChina
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationHUTCHMED Limited
B.5.2Functional name of contact pointMark Woods
B.5.3 Address:
B.5.3.1Street AddressBuilding 4, 720 Cailun Road, China (Shanghai) Pilot Free Trade Zone
B.5.3.2Town/ cityShanghai
B.5.3.3Post code201203
B.5.3.4CountryChina
B.5.4Telephone number34961244000 Ext 411532
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameSurufatinib
D.3.2Product code HMPL-012
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation Yes
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNSURUFATINIB
D.3.9.1CAS number 1308672-74-3
D.3.9.2Current sponsor codeHMPL-012
D.3.9.4EV Substance CodeSUB194701
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameSurufatinib
D.3.2Product code HMPL-012
D.3.4Pharmaceutical form Capsule, hard
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNSURUFATINIB
D.3.9.1CAS number 1308672-74-3
D.3.9.2Current sponsor codeHMPL-012
D.3.9.4EV Substance CodeSUB194701
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number50
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Gemcitabine 100 mg/ml Concentrate for Solution for Infusion
D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Limited
D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameGemcitabine
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNGemcitabine
D.3.9.3Other descriptive nameGEMCITABINE HYDROCHLORIDE
D.3.9.4EV Substance CodeSUB02324MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number100
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
recurrent or refractory solid tumors or lymphoma (not central nervous system) who have a known or expected dysfunction of vascular endothelial growth factor receptor-1, -2, and -3; fibroblast growth factor receptor 1, or CSF-1R pathways
tumores sólidos o linfomas recurrentes o refractarios (que no se encuentren en el
sistema nervioso central) que tengan una disfunción confirmada o esperada del
receptor del factor de crecimiento endotelial vascular 1, 2 y 3, del receptor del factor
de crecimiento de fibroblastos 1 o de las vías del receptor del factor estimulante de
colonias 1 (CSF-1R).
E.1.1.1Medical condition in easily understood language
recurrent or refractory solid tumors or lymphoma
tumores sólidos recurrentes o refractarios
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10065147
E.1.2Term Malignant solid tumor
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10025310
E.1.2Term Lymphoma
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10015564
E.1.2Term Ewing's sarcoma recurrent
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.0
E.1.2Level PT
E.1.2Classification code 10039027
E.1.2Term Rhabdomyosarcoma recurrent
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 22.1
E.1.2Level LLT
E.1.2Classification code 10082652
E.1.2Term Non-rhabdomyosarcoma soft-tissue sarcoma
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10031296
E.1.2Term Osteosarcoma recurrent
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
Part 1
To determine MTD and/or RP2D of surufatinib, and to evaluate the safety and tolerability of surufatinib in combination with gemcitabine in pediatric patients with recurrent or refractory solid tumors or lymphoma
Part 2
To evaluate the DCR in pediatric patients with osteosarcoma and the ORR in pediatric patients with Ewing sarcoma and RMS, NRSTS and other tumor types as per emerging data from part 1 of the study, when treated with the combination of surufatinib and gemcitabine
Parte 1 Determinar la DMT o la dosis recomendada para la fase II (DRF2) del
surufatinib y evaluar la seguridad y la tolerabilidad del surufatinib en combinación
con la gemcitabina en pacientes pediátricos con tumores sólidos o linfoma
recurrentes o refractarios Parte 2 Evaluar la TCE en pacientes pediátricos con
osteosarcoma y la TRO en pacientes pediátricos con sarcoma de Ewing y RMS,
SPBNR y otros tipos de tumores según los datos que se obtengan en la parte 1 del
estudio, cuando se tratan con la combinación de surufatinib y gemcitabina
E.2.2Secondary objectives of the trial
Part 1
To characterize the PK of surufatinib as a monotherapy and in combination with gemcitabine in pediatric patients
To document the PK exposure of gemcitabine when used in combination with surufatinib
To evaluate the anti-tumor activity of surufatinib in combination with gemcitabine in pediatric patients
Acceptability and palatability of surufatinib oral suspension
Part 2
To evaluate other anti-tumor activity of the combination of surufatinib and gemcitabine in pediatric patients as per emerging data from part 1 of the study
To evaluate the safety and tolerability of surufatinib in combination with gemcitabine in pediatric patients as per emerging data from part 1 of the study
To characterize the PK of surufatinib and in combination with gemcitabine in pediatric patients as per emerging data from part 1 of the study
To document the PK exposure of gemcitabine when used in combination with surufatinib
Acceptability and palatability of surufatinib oral suspension
Parte 1 Caracterizar la FC de surufatinib en monoterapia y en combinación la gemcitabina en pacientes pediátricos. Documentar la exposición FC de la gemcitabina cuando se usa en combinación con el surufatinib. Evaluar la actividad
antitumoral de surufatinib en combinación con gemcitabina en pacientes pediátricos. Aceptabilidad y agradabilidad de surufatinib en suspensión oral. Parte 2 Evaluar otra actividad antitumoral de la combinación de surufatinib y gemcitabina en pacientes pediátricos según datos que se obtengan en la parte 1 del estudio.
Evaluar la seguridad y la tolerabilidad de surufatinib en combinación con gemcitabina en pacientes pediátricos según datos que se obtengan en la parte 1 .
Caracterizar la FC del surufatinib y en combinación con gemcitabina en pacientes
pediátricos según datos que se obtengan en la parte 1 . Documentar la exposición
FC de gemcitabina cuando se usa en combinación con surufatinib. Aceptabilidad y
agradabilidad de surufatinib en suspensión oral
E.2.3Trial contains a sub-study No
E.2.3.1Full title, date and version of each sub-study and their related objectives
1. Edad: En el momento de la inscripción en el estudio, los pacientes deben tener a.
Parte 1 (incluida la cohorte de expansión PK): desde el nacimiento hasta <18 años
de edad; b. Parte 2: desde el nacimiento hasta <18 años de edad (salvo lo indicado
a continuación); Nota: Los pacientes <2 años de edad sólo se inscribirán en
Europa, sin embargo, la inscripción de pacientes <2 años de edad no comenzará
hasta que se disponga de datos definitivos de toxicidad en animales juveniles. 2.
Diagnóstico a. Parte 1 - Son elegibles los pacientes con cualquier tumor sólido o
linfoma recurrente o refractario (no del SNC) que tengan una disfunción conocida o
esperada de las vías VEGFR-1, -2 y -3; FGFR-1 o CSF-1R (según la literatura). Los
pacientes deben tener verificación histológica de malignidad en el diagnóstico
original o en la recaída. b. Parte 2 - Osteosarcoma recurrente o refractario, sarcoma
de Ewing, RMS o NRSTS (sólo en la UE y el Reino Unido). Los pacientes deben
haber tenido una verificación histológica de malignidad en el diagnóstico original o
en la recaída. 3. Estado de la enfermedad: Los pacientes deben tener una
enfermedad medible o evaluable para el aumento de dosis de la parte 1; para laparte 2, los pacientes deben tener una enfermedad medible según la versión 1.1 de
RECIST. 4. Opciones terapéuticas: El estado actual de la enfermedad del paciente
debe ser uno para el que no exista una terapia curativa conocida. 5. Nivel de
rendimiento: Karnofsky #50 para pacientes #16 y <18 años de edad y Lansky #50
para pacientes <16 años de edad (véase el Apéndice 1 del protocolo del estudio),
Eastern Cooperative Oncology Group (ECOG) #2 para pacientes #18 años de
edad. (Nota: Los pacientes que no puedan caminar debido a una parálisis, pero que
utilicen una silla de ruedas, se considerarán ambulatorios a efectos de evaluar la
puntuación de rendimiento). Para más detalles sobre los criterios de inclusión,
consulte el protocolo del estudio.
E.3Principal inclusion criteria
1. Age: At time of study enrollment, patients must be
a. Part 1 (including PK expansion cohort): from birth to <18 years of age;
b. Part 2: from birth to <18 years of age (except as noted below);
Note: Patients <2 years of age will only be enrolled in Europe, however, enrollment of patients <2 years of age will not begin until definitive juvenile animal toxicity data is available.
2. Diagnosis
a. Part 1 – Patients with any recurrent or refractory solid tumors or lymphoma (not CNS) that have a known or expected dysfunction of VEGFR-1, -2, and -3; FGFR-1, or CSF-1R pathways (based on literature) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
b. Part 2 – Recurrent or refractory osteosarcoma, Ewing sarcoma, RMS, or NRSTS (EU/UK only). Patients must have had histologic verification of malignancy at original diagnosis or relapse.
3. Disease status: Patients must have measureable or evaluable disease for part 1 dose escalation; for part 2, patients must have measurable disease by RECIST version 1.1.
4. Therapeutic options: Patient’s current disease state must be one for which there is no known curative therapy.
5. Performance level: Karnofsky ≥50 for patients ≥16 and <18 years of age and Lansky ≥50 for patients <16 years of age (see Appendix 1 of the study protocol), Eastern Cooperative Oncology Group (ECOG) ≤2 for patients ≥18 years of age. (Note: Patients who are unable to walk because of paralysis, but who are using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.)
For further details regarding inclusion criteria please refer to the study protocol.
1. Edad: En el momento de la inscripción en el estudio, los pacientes deben tener a.
Parte 1 (incluida la cohorte de expansión PK): desde el nacimiento hasta <18 años
de edad; b. Parte 2: desde el nacimiento hasta <18 años de edad (salvo lo indicado
a continuación); Nota: Los pacientes <2 años de edad sólo se inscribirán en
Europa, sin embargo, la inscripción de pacientes <2 años de edad no comenzará
hasta que se disponga de datos definitivos de toxicidad en animales juveniles. 2.
Diagnóstico a. Parte 1 - Son elegibles los pacientes con cualquier tumor sólido o
linfoma recurrente o refractario (no del SNC) que tengan una disfunción conocida o
esperada de las vías VEGFR-1, -2 y -3; FGFR-1 o CSF-1R (según la literatura). Los
pacientes deben tener verificación histológica de malignidad en el diagnóstico
original o en la recaída. b. Parte 2 - Osteosarcoma recurrente o refractario, sarcoma
de Ewing, RMS o NRSTS (sólo en la UE y el Reino Unido). Los pacientes deben
haber tenido una verificación histológica de malignidad en el diagnóstico original o
en la recaída. 3. Estado de la enfermedad: Los pacientes deben tener una
enfermedad medible o evaluable para el aumento de dosis de la parte 1; para la parte 2, los pacientes deben tener una enfermedad medible según la versión 1.1 de
RECIST. 4. Opciones terapéuticas: El estado actual de la enfermedad del paciente
debe ser uno para el que no exista una terapia curativa conocida. 5. Nivel de
rendimiento: Karnofsky #50 para pacientes #16 y <18 años de edad y Lansky #50
para pacientes <16 años de edad (véase el Apéndice 1 del protocolo del estudio),
Eastern Cooperative Oncology Group (ECOG) #2 para pacientes #18 años de
edad. (Nota: Los pacientes que no puedan caminar debido a una parálisis, pero que
utilicen una silla de ruedas, se considerarán ambulatorios a efectos de evaluar la
puntuación de rendimiento). Para más detalles sobre los criterios de inclusión,
consulte el protocolo del estudio.
E.4Principal exclusion criteria
1. Pregnancy or breastfeeding: Pregnant or breastfeeding females will not be entered into this study due to risks of fetal and teratogenic AEs as seen in animal toxicity studies. Pregnancy tests must be obtained in females who are postmenarchal.
2. Concomitant medications
a. Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible (if used to modify immune AEs related to prior therapy, ≥14 days must have elapsed since last dose of corticosteroid).
b. Investigational drugs: patients who are currently receiving another investigational drug are not eligible.
c. Anticancer agents: patients who are currently receiving other anticancer agents are not eligible.
d. QTc agents: patients who are receiving drugs that prolong QTc within the last 7 days are not eligible.
e. Patients may not be on clozapine, natalizumab, leflunomide, tofacitinib, or warfarin as these may interact with gemcitabine.
f. Patients who are receiving medications that are strong inhibitors or inducers of CYP3A4
3. Thyroid replacement therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 3 weeks prior to study enrollment.
4. Patients who have uncontrolled infection are not eligible.
5. Patients who have major surgery or significant traumatic injury within 28 days of the first dose of study treatment are not eligible.
a. Central line placement or subcutaneous port placement is not considered major surgery. External central lines must be placed at least 3 days prior to enrollment and subcutaneous ports must be placed at least 7 days prior to enrollment.
For further details regarding exclusion criteria please refer to the study protocol.
1. Embarazo o lactancia: Las mujeres embarazadas o en periodo de lactancia no
participarán en este estudio debido a los riesgos de EA fetales y teratogénicos
observados en los estudios de toxicidad en animales. Se deben obtener pruebas de
embarazo en las hembras postmenárquicas. 2. Medicamentos concomitantes a.
Corticosteroides: los pacientes que reciban corticosteroides y que no hayan
recibido una dosis estable o decreciente de corticosteroides durante al menos 7
días antes de la inscripción no son elegibles (si se utilizan para modificar los EA
inmunes relacionados con la terapia anterior, deben haber transcurrido #14 días
desde la última dosis de corticosteroides). b. Fármacos en investigación: los pacientes que están recibiendo actualmente otro fármaco en investigación no son
elegibles. c. Agentes anticancerígenos: los pacientes que estén recibiendo
actualmente otros agentes anticancerígenos no son elegibles. d. Agentes QTc: los
pacientes que estén recibiendo fármacos que prolonguen el QTc en los últimos 7
días no son elegibles. e. Los pacientes no pueden estar tomando clozapina,
natalizumab, leflunomida, tofacitinib o warfarina, ya que pueden interactuar con la
gemcitabina. f. Pacientes que estén recibiendo medicamentos que sean fuertes
inhibidores o inductores del CYP3A4. 3. 3. Terapia de reemplazo de la tiroides: Los
pacientes que requieren terapia de reemplazo de la tiroides no son elegibles si no
han estado recibiendo una dosis de reemplazo estable durante al menos 3
semanas antes de la inscripción en el estudio. 4. Los pacientes que tengan una
infección no controlada no son elegibles. 5. 5. Los pacientes que tengan una cirugía
mayor o una lesión traumática significativa dentro de los 28 días de la primera dosis
del tratamiento del estudio no son elegibles. a. La colocación de una vía central o
de un puerto subcutáneo no se considera una cirugía mayor. Las líneas centrales
externas deben colocarse al menos 3 días antes de la inscripción y los puertos
subcutáneos deben colocarse al menos 7 días antes de la inscripción. Para más
detalles sobre los criterios de exclusión, consulte el protocolo del estudio
E.5 End points
E.5.1Primary end point(s)
Part 1
• The incidence of dose limiting toxicities in each dose level
• Safety, as assessed by:
o The frequency and severity of AEs
o Physical examination findings
o Vital signs
o Laboratory test results
o 12-lead ECG
Part 2
• DCR at 16 weeks for patients with osteosarcoma
• ORR at 14 weeks for patients with Ewing sarcoma, RMS, and NRSTS
Parte 1 • Incidencia de toxicidades limitantes de la dosis en cada nivel de dosis •
Seguridad, evaluada mediante lo siguiente o La frecuencia y la gravedad de los
acontecimientos adversos (AA) o Hallazgos de las exploraciones físicas o
Constantes vitales o Resultados de las pruebas analíticas o Electrocardiograma
(ECG) de 12 derivaciones Parte 2 TCE a las 16 semanas en el caso de los
pacientes con osteosarcoma TRO a las 14 semanas en pacientes con sarcoma de
Ewing, RMS y SPBNR
E.5.1.1Timepoint(s) of evaluation of this end point
Part 1:
Dose Limiting Toxicity: Cycle 1 (35 days)
Safety: from date of consent to 30 days after the last dose.
Part 2:
• DCR at 16 weeks for patients with osteosarcoma
• ORR at 14 weeks for patients with Ewing sarcoma, RMS, and NRSTS
Parte 1: Toxicidad limitante de la dosis: Ciclo 1 (35 días) Seguridad: desde la fecha
de consentimiento hasta 30 días después de la última dosis. Parte 2: - TCE a las 16
semanas para pacientes con osteosarcoma - TRO a las 14 semanas para pacientes con sarcoma de Ewing, RMS y NRSTS
E.5.2Secondary end point(s)
Part 1
• Observed plasma concentrations of surufatinib and estimated population PK and exposure parameters for surufatinib
• Pharmacokinetic parameters for the dose escalation and PK expansion cohorts: Cmax, Tmax, AUC, Cmin, effective T1/2, CL/F, and accumulation ratio
• Observed plasma concentrations of gemcitabine
• Efficacy endpoints evaluated per RECIST version 1.1:
o ORR
o DCR
o TTR
o Duration of response (DoR)
o PFS
• The taste and palatability survey

Part 2
• TTR
• DoR
• PFS
• Safety, as assessed by:
o Frequency and severity of AEs
o Physical examination findings
o Vital signs
o Laboratory test results
o 12-lead ECG
• Observed plasma concentrations of surufatinib and estimated population PK and exposure parameters for surufatinib
• Observed plasma concentrations of gemcitabine
• The taste and palatability survey
Concentraciones plasmáticas observadas del surufatinib y parámetros estimados
de farmacocinética poblacional y exposición del surufatinib • Parámetros
farmacocinéticos para las cohortes de aumento de la dosis y de ampliación de la
FC: concentración plasmática máxima (Cmáx), tiempo hasta alcanzar la
concentración plasmática máxima (Tmáx), área bajo la curva de concentración
plasmática-tiempo (ABC), concentración plasmática mínima (Cmín), semivida
efectiva (t½), aclaramiento total aparente del plasma tras la administración oral
(CL/F) y proporción de acumulación • Concentraciones plasmáticas observadas de
la gemcitabina Criterios de valoración de la eficacia evaluados según la versión 1.1
de los criterios de evaluación de la respuesta en tumores sólidos (RECIST): o La
tasa de remisión objetiva (TRO) - Tasa de control de la enfermedad (TCE) - Tiempo
hasta la respuesta (THR) - Duración de la respuesta (DR) - Supervivencia sin
progresión (SSP) - Encuesta de sabor y agradabilidad
E.5.2.1Timepoint(s) of evaluation of this end point
Part 1:
Surufatinib PK: from Cycle 1 to last cycle
Gemcitabine PK: Cycle 1
Efficacy: from start of treatment till the end of treatment
The taste and palatability survey: C1D1 and C1D8
Part 2:
Efficacy and Safety: from start of treatment till the end of treatment
Taste survey: C1D1 and C1D8
Surufatinib PK: from Cycle 1 to last cycle
Gemcitabine PK: Cycle 1
The taste and palatability survey: C1D1 and C1D8
Parte 1: FC de Surufatinib PK: del ciclo 1 al último ciclo FC de gemcitabina: Ciclo 1
Eficacia: desde el inicio del tratamiento hasta el final del tratamiento La encuesta de
sabor y agradabilidad: C1D1 y C1D8 Parte 2: Eficacia y Seguridad: desde el inicio
del tratamiento hasta el final del tratamiento Encuesta gustativa: C1D1 y C1D8 FC
de Surufatinib PK: del ciclo 1 al último ciclo FC de gemcitabina: Ciclo 1 La encuesta
de sabor y agradabilidad: C1D1 y C1D8
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Acceptability and palatability of surufatinib oral suspension, biomarkers
Aceptabilidad y agradabilidad de la suspensión oral de surufatinib, biomarcadores
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) Yes
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other Yes
E.7.1.3.1Other trial type description
Part 1 - dose escalation study to determine recommended phase 2 dose in pediatric patients
Parte 1: estudio de escalada de dosis para determinar la dosis de fase 2 recomendada en pacientes pe
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled No
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Parte 1 - diseño de 6 rodillos; Parte 2 - diseño de 2 etapas de Simon
Part 1 - rolling 6 design; Part 2 - Simon 2-stage design
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other No
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned2
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA13
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Denmark
France
Germany
Italy
Netherlands
Spain
United Kingdom
United States
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
LVLS
Última visita del último paciente
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years3
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 116
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) Yes
F.1.1.4.1Number of subjects for this age range: 2
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 34
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 80
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
minors (from birth)
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state13
F.4.2 For a multinational trial
F.4.2.1In the EEA 41
F.4.2.2In the whole clinical trial 116
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
In both parts 1 and 2, patients can remain on treatment until completing cycle 17, or until progressive disease, unacceptable toxicity, or death; whichever comes first. If any patient completes 17 cycles and is still benefiting from study treatment, the Principal Investigator (PI) and Sponsor may discuss options that allow the patient to continue to receive treatment.
Tanto en la parte 1 como en la 2, los pacientes pueden seguir recibiendo el tratamiento hasta completar el ciclo 17, o hasta que la enfermedad progrese, tenga una toxicidad inaceptable o muera; lo que ocurra primero. Si algún paciente completa 17 ciclos y sigue beneficiándose del tratamiento del estudio, el investigador principal (IP) y el promotor podrán discutir opciones que permitan al
paciente seguir recibiendo el tratamiento
G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1Name of Organisation COG, Children's Oncology Group
G.4.3.4Network Country United States
G.4 Investigator Network to be involved in the Trial: 2
G.4.1Name of Organisation ITCC, Innovative Therapies for Children with Cancer in Europe
G.4.3.4Network Country France
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-09-16
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-06-24
P. End of Trial
P.End of Trial StatusOngoing