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    Summary
    EudraCT Number:2020-006118-19
    Sponsor's Protocol Code Number:2020-012-00EU1
    National Competent Authority:Norway - NOMA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-03-03
    Trial 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
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNorway - NOMA
    A.2EudraCT number2020-006118-19
    A.3Full title of the trial
    An Open-Label Phase 2 Study of Surufatinib in Patients with Neuroendocrine Tumours in Europe
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open-Label Phase 2 Study of Surufatinib in Patients with Neuroendocrine Tumours in Europe
    A.4.1Sponsor's protocol code number2020-012-00EU1
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04579679
    A.5.4Other Identifiers
    Name:Investigational New Drug (IND)Number:124522
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    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 pointNick Lawn
    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+1973826 2891
    B.5.6E-mailnickl@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 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.3.9.3Other descriptive nameSurufatinib
    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.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
    Neuroendocrine Tumours
    E.1.1.1Medical condition in easily understood language
    Neuroendocrine Tumours
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10052399
    E.1.2Term Neuroendocrine tumour
    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
    To evaluate the antitumor activity of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well differentiated neuroendocrine tumors (NETs)
    E.2.2Secondary objectives of the trial
    - To characterise the PK of surufatinib in patients with NET
    - To evaluate the effect of surufatinib on cardiac repolarisation, as detected by changes in ECG corrected QTc, and the potential relationship with surufatinib plasma concentrations
    - To further characterise the antitumour activity of surufatinib in patients with NET
    - Cohort D only: To evaluate the effects of repeat dosing of surufatinib on the single-dose PK of cytochrome P450 (CYP)3A4, P glycoprotein (P gp), and breast cancer resistance protein (BCRP) substrates in patients with NET
    - To evaluate the safety and tolerability of surufatinib in patients with NET
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Cohort D (Drug-Drug Interaction [DDI] Sub-Study): The primary objective of this cohort is to investigate the potential DDI between surufatinib and a drug cocktail containing selective probes of CYP3A4 (midazolam), Pgp (fexofenadine), and BCRP (rosuvastatin) substrates.
    E.3Principal inclusion criteria
    1. Has histologically or cytologically documented, locally advanced, or metastatic low- to intermediate-grade (grades 1 to 2) NETs and has progressed on at least 1 prior line of therapy, but no more than 3 therapies:
    a. Cohort A: NET of lung origin
    b. Cohort B: NET of small bowel origin
    c. Cohort C: NET of non-small bowel, non-pancreas, and non-lung origin
    d. Cohort D (DDI substudy): NET of any origin
    2. Has radiologic evidence of progressive tumor within 12 months of study enrolment
    3. Is willing and able to provide informed consent
    4. Is ≥18 years of age
    5. Has measurable lesions according to RECIST Version 1.1
    6. Has absolute neutrophil count of ≥ 1.5×10^9/L, platelet count of ≥ 100×10^9/L, and hemoglobin of ≥ 9 g/dL
    7. Has serum total bilirubin of <1.5 times the upper limit of normal (ULN)
    8. Has proteinuria of <2+ by urinalysis, or 24-hour urine collection of ≤1 g of protein, or urine protein: urine-creatinine ratio of ≤1.9
    9. Has ALT, AST or alkaline phosphatase (ALP) levels of ≤ 2.5 times the ULN
    a. Patients with known liver metastases may have ALT, AST, and ALP of ≤3× the ULN
    10. Has serum creatinine of <1.5 times ULN or creatinine clearance of ≥ 60 mL/min
    11. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    12. Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include oral, progestogen-only, hormonal contraception (combined estrogen/progestogen should be avoided) or highly effective non-oral hormonal contraception (e.g., Depo-Provera and Implanon) associated with inhibition of ovulation together with a barrier method (e.g., diaphragm, always containing a spermicide), intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner, or sexual abstinence in line with the preferred and usual lifestyle of the subject. Oral and non-oral hormonal contraception should always be combined with an additional contraceptive method (i.e., barrier method) because of a potential interaction with the study drug. The same criteria are applicable to male patients involved in this clinical study if they have a partner of childbearing potential, and male patients must always use a condom.
    A female is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (ie, ≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of the ovaries and/or uterus).
    E.4Principal exclusion criteria
    1. Has an AE due to previous antitumor therapy that has not recovered to CTCAE Grade ≤1, except alopecia and peripheral neurotoxicity with CTCAE Grade ≤2 caused by platinum chemotherapy
    2. Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment. Prior palliative radiotherapy for metastatic lesions is permitted if there is at least 1 measurable lesion that has not been irradiated.
    3. Prior VEGF/VEGFR-targeted therapy, including, but not limited to sunitinib, axitinib, and cabozantinib
    4. Has uncontrollable hypertension, defined as systolic blood pressure of ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg, despite antihypertensive medication
    5. Prothrombin time (PT)/International normalized ratio (INR) of >1.5 or activated partial thromboplastin time (aPTT) of >1.5×ULN (for patients on Coumadin or coumadin-like products)
    6. Has gastrointestinal disease or condition within 6 months prior to first dose that investigators suspect may affect drug absorption, including, but not limited to, active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that could, in the investigators judgment, result in bleeding or perforation
    7. Has a history or presence of a serious hemorrhage (>30 mL within 3 months) or hemoptysis (>5 mL of blood within 4 weeks) within 6 months of first dose of study drug
    8. Has clinically significant cardiovascular disease, including, but not limited to, acute myocardial infarction within 6 months prior to enrolment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure of ≥2 according to the New York Heart Association classification, ventricular arrhythmia that needs drug treatment, and left ventricular ejection fraction (LVEF) of <50%
    9. Has a mean corrected QT interval by Fridericia (QTcF) of ≥480 ms
    10. Has used medication known to cause QT prolongation or torsades de pointes within 2 weeks of screening
    11. Has brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease (SD) for 14 days or longer; patients requiring steroids within 4 weeks prior to start of study treatment will be excluded
    12. Has a high risk of bleeding at screening due to tumor invasion into major vessels, such as pulmonary artery, the superior vena cava, or the inferior vena cava, as determined by investigators
    13. Has arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic events (including stroke and/or transient ischemic attack) within 6 months prior to the first dose of study drug
    14. Use of strong or moderate inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of surufatinib
    15. For Cohort D, use of medications that are known substrates, inhibitors, or inducers of CYP3A or substrates of P-gp or BCRP within 3 weeks before the first dose of the drug cocktail
    16. Prior history of other cancer except those treated with curative intent for in situ non-melanoma skin cancer, breast, or cervical cancer, or those treated with curative intent and no evidence of disease in the last 5 years prior to enrolment in the study
    17. Has a clinically meaningful ongoing infection (eg, requiring intravenous treatment with anti-infective therapy)
    a. See Appendix 8 (Section 15) for procedures specific to subjects with suspected or confirmed coronavirus disease 2019 (COVID-19)
    18. Has clinical symptoms consistent with pancreatitis
    19. Has a history of allergies to any ingredient of surufatinib or its capsule shell, including tartrazine (E 102)
    20. Pregnant or breastfeeding females will not be entered into this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies (pregnancy tests must be obtained in females who are of reproductive potential)
    E.5 End points
    E.5.1Primary end point(s)
    Disease Control Rate (DCR) at 6 months
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months
    E.5.2Secondary end point(s)
    - Observed plasma concentrations, estimated population PK, and exposure parameters of surufatinib
    - QTc and plasma concentrations of surufatinib at specified time points
    - Additional efficacy endpoints
    • Objective Response Rate (ORR)
    • Time to Response (TTR)
    • Duration of Response (DoR)
    • Progressive-Free Survival (PFS)
    - Cohort D only: Exposure parameters of CYP3A4, P-gp, and BCRP substrates
    - Safety assessments include:
    • Frequency and severity of AEs
    • Physical examination findings
    • Vital signs
    • Laboratory tests
    • ECG
    • Echocardiograms/MUGA
    E.5.2.1Timepoint(s) of evaluation of this end point
    PK Plasma Sampling: Day (-1 & -2) & at specific timepoints as per Schedule of Events (SOE)
    ECG for QTc Evaluation: At pre & post-dose on Cycle 1 Day 1 and Cycle 1 Day 15 (+1 week) at specific time points given in SOE
    ORR: Time to attain best overall response or CR or PR per RECIST Version 1.1
    TTR: Time between the start date of study drug until first documented response (CR or PR) according to RECIST Version 1.1
    DoR: Timepoint at which the objective response reaches CR or PR, whichever comes first, until the occurrence of PD or death
    PFS: Time from the start of study drug to date of objective disease progression as defined by RECIST Version 1.1 or death, whichever comes first.
    Echocardiogram/MUGA: At screening, Every 12 weeks (±7 days) after the first dose
    AEs, SAEs: Screening, EOT
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    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
    Tolerability, Drug-drug interaction (DDI)
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    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 No
    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 EEA16
    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
    Spain
    Germany
    Italy
    Norway
    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 years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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 No
    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) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 46
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 72
    F.4.2.2In the whole clinical trial 78
    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)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-05-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-02-04
    P. End of Trial
    P.End of Trial StatusOngoing
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