Clinical Trial Page

Summary
EudraCT Number:2021-003602-41
Sponsor's Protocol Code Number:2020-012-GLOB2
National Competent Authority:Germany - BfArM
Clinical Trial Type:EEA CTA
Trial Status:Prematurely Ended
Date on which this record was first entered in the EudraCT database:2022-07-01
Trial results View results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedGermany - BfArM
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
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
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 number+441494630622
B.5.6E-mailmarkw@hutch-med.com
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
E.1.1.1Medical condition in easily understood language
recurrent or refractory solid tumors or lymphoma
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
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
E.2.3Trial contains a sub-study No
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.
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.
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
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
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
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
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
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
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
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 Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
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
United States
France
Netherlands
Spain
Germany
Italy
Denmark
United Kingdom
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
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 state5
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.
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 Decision2022-09-23
N.Ethics Committee Opinion of the trial application
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion
P. End of Trial
P.End of Trial StatusPrematurely Ended
P.Date of the global end of the trial2023-04-25

Sponsors and Collaborators

Medical Conditions

Drug Interventions

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