Neuroendocrine TumoursPhase 2NCT04579679
Open-Label Surufatinib in European Patients With NET
A Phase 2 study testing Surufatinib in people with Neuroendocrine Tumours and Neuroendocrine Tumour of the Lung, run by Hutchmed at 23 sites in 7 countries.
Trial summary
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumours, Neuroendocrine Tumour of the Lung, Small Intestinal NET
- What is being tested?
- Surufatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 23 sitesin 7 countries
- Study dates
- 13 Aug 2021to 15 Oct 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies;
- Has radiologic evidence of progressive tumour within 12 months of study enrolment
- Is willing and able to provide informed consent
- Is ≥18 years of age
- Has measurable lesions according to RECIST Version 1.1
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception
Who cannot join
- Has an AE due to previous anti-tumour therapy that has not recovered to ≤CTCAE Grade 1, except alopecia and peripheral neurotoxicity with ≤CTCAE Grade 2 caused by platinum chemotherapy
- Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment.
- Prior VEGF/VEGFR-targeted therapy
- Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication
- Gastrointestinal disease or condition within 6 months prior to first dose
- Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks) within 6 months of first dose of study drug.
Show all 11Show fewer
- Clinically significant cardiovascular disease.
- 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.
- A high risk of bleeding at screening due to tumour invasion into major vessels, such as pulmonary artery, the superior vena cava, or the inferior vena cava, as determined by investigators.
- Has arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic events (including stroke and/or transient ischaemic attack) within 12 months.
- Has a clinically meaningful ongoing infection (eg, requiring intravenous treatment with anti-infective therapy)
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
United States5 sites
Emory University, Winship Cancer Institute
Atlanta, Georgia, 30322-1013
University of Alabama, Birmingham (UAB)
Birmingham, Alabama, 35233
Houston Methodist
Houston, Texas, 77030
University of California Irvine Medical Center UCIMC - H.H. Chao Comprehensive Digestive Disease Center CDDC
Orange, California, 92868
Stony Brook Cancer Center
Stony Brook, New York, 11794
Spain5 sites
Institut Catala d'Oncologis (ICO) - Hospital Duran i Reynals
Barcelona, 8013
Hospital Vall Hebron
Barcelona, 8035
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Virgen del Rocio
Seville, 41013
Italy4 sites
Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari
Bari, 70124
ASST-Spedali Civili di Brescia
Brescia, 25123
Universita degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi (AOUC)
Florence, 50134
Istituto Europeo di Oncologia
Milan, 20141
Germany3 sites
Charite Universitatsmedizin Berlin
Berlin, 13353
Universitaetsklinikum Erlangen
Erlangen, 91054
Universitatsklinikum Essen, Klinik fur Endokrinologie
Essen, 45147
France2 sites
CHU Bordeaux
Pessac, 33604
Institut Gustave Roussy
Villejuif, 94800
Norway2 sites
Haukeland University Hospital
Bergen, 5021
Oslo University Hospital Rikshospitalet
Oslo, 0372
United Kingdom2 sites
Sarah Cannon Research Institute
London, W1G 6AD
Christie Hospital
Manchester, M20 4BX
About this study
Official title: An Open-Label Phase 2 Study of Surufatinib in Patients With Neuroendocrine Tumours in Europe
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs).
Read the detailed description
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated NETs.
The study will enroll 4 cohorts of varying NETs, as follows:
- Cohort A - NET of lung origin
- Cohort B - NET of small bowel origin
- Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin
- Cohort D - NET of any origin (DDI substudy)
All patients will be treated with oral surufatinib 300 mg QD in treatment cycles of 28 days starting on Cycle 1 Day 1.
- Being tested
- Surufatinib
- Keywords
- VEGF
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurufatinibDrug
Also called HMPL-012, sulfatinib
Surufatinib 300 mg oral once daily
| Study group | Role | What they receive |
|---|---|---|
| Surufatinib | Experimental | Cohorts A, B, and C: oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1
Cohort D:
Surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day and single doses of drug cocktail on Day-2 and Day 15 Cycle 1 Receives: Drug: Surufatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate (DCR)
The DCR was defined as the percentage of patients who achieved a best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study.
Measured: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Secondary outcomes (8)
Plasma Concentrations of Surufatinib
Blood samples were collected at specified timepoints to obtain plasma concentrations of surufatinib at steady state on Cycle 1 Day 15.
Measured: Cohorts A, B and C: Pre-dose and 1, 2, 3, 4 hours post-dose on Cycle 1 Day 15; Cohort D: Pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8 and 10 hours post-dose on Cycle 1 Day 15
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment
The QT interval data was corrected for heart rate using 2 correction methods (Fridericia - QTcF and Bazett - QTcB). The treatment period was defined as the period from first administration of study drug up 30 days after last administration. msec=milliseconds, IFB=increase from baseline.
Measured: From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
Objective Response Rate (ORR)
The ORR was defined as the percentage of patients with a BOR of CR or PR as determined by the Investigator using RECIST v1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Time to Response (TTR)
The TTR was defined as the time from the start of study drug until the date of first documented objective response, either CR or PR (whichever was recorded first) according to RECIST v.1.1 for responders only. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Duration of Response (DOR)
The DoR was defined as the time from the first time that the objective response reached CR or PR, whichever came first (and later confirmed), until the occurrence of PD or death. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of 1 or more new lesions was also considered progression.
Measured: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Progression-Free Survival (PFS)
The PFS was defined as the time from the start of study drug until the first objective PD as defined by RECIST v1.1 or death, whichever came first. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of 1 or more new lesions was also considered progression.
Measured: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline
Participants were administered midazolam, fexofenadine and rosuvastatin (as part of the drug cocktail) as a single dose on Day -2 (without surufatinib) and on Cycle 1 Day 15 (with surufatinib). Separate blood samples were collected for measurement of plasma concentrations of each probe substrate and surufatinib. Probe substrate of midazolam was CYP3A4, fexofenadine was P-gp and rosuvastatin was BCRP. Ratio of LS Mean for maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) are presented as Cycle 1 Day 15/Day -2.
Measured: Baseline (Day -2) and Cycle 1 Day 15
Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An AE is any untoward medical occurrence in a clinical study patient temporally associated with the use of a study drug, whether or not considered related to the drug. An SAE was an AE that resulted in any of the following outcomes: death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect or was any important medical event. TEAEs were defined as any AEs that started or worsened in severity on or after the first administration date of study drug and no later than 30 (+7) days after the last administration date of study drug or initiation of new anti-tumor therapy (whichever occurred first).
Measured: From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start13 Aug 2021
- Primary completion6 Sep 2024
- Study completion15 Oct 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuroendocrine TumoursStudies of the same condition, open and under way.
- More trials run by HutchmedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Schelman, MD, PhD, Study director, Hutchmed
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04579679
- Sponsor's protocol ID
- 2020-012-00EU1
- Status last verified
- Jul 2025
- First submitted
- 23 Sep 2020
- Last updated
- 25 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase 2 Study of Surufatinib in Patients With Neuroendocrine Tumours in Europe
- ClinicalTrials.gov ID
- NCT04579679
- Acronym / sponsor ID
- 2020-012-00EU1
- Keywords
- VEGF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 78 participants (actual)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 13 Aug 2021 (actual)
- Primary completion
- 6 Sep 2024 (actual)
- Study completion
- 15 Oct 2024 (actual)
- First posted
- 8 Oct 2020 (actual)
- Results
- Posted 25 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low to intermediate grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumours (NETs).
Detailed description
This is a Phase 2, open-label, multi-centre study of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated NETs.
The study will enroll 4 cohorts of varying NETs, as follows:
- Cohort A - NET of lung origin
- Cohort B - NET of small bowel origin
- Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin
- Cohort D - NET of any origin (DDI substudy)
All patients will be treated with oral surufatinib 300 mg QD in treatment cycles of 28 days starting on Cycle 1 Day 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surufatinib | Experimental | Drug: SurufatinibCohorts A, B, and C: oral surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day1 Cohort D: Surufatinib 300 mg once daily in treatment cycles of 28 days starting at Cycle 1 Day and single doses of drug cocktail on Day-2 and Day 15 Cycle 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies;
- Has radiologic evidence of progressive tumour within 12 months of study enrolment
- Is willing and able to provide informed consent
- Is ≥18 years of age
- Has measurable lesions according to RECIST Version 1.1
Key exclusion criteria (11 listed)
- Has an AE due to previous anti-tumour therapy that has not recovered to ≤CTCAE Grade 1, except alopecia and peripheral neurotoxicity with ≤CTCAE Grade 2 caused by platinum chemotherapy
- Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment.
- Prior VEGF/VEGFR-targeted therapy
- Uncontrollable hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, despite antihypertensive medication
- Gastrointestinal disease or condition within 6 months prior to first dose
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SurufatinibAlso: HMPL-012, sulfatinibSurufatinib 300 mg oral once daily | Drug | Surufatinib |
Primary outcome
Disease Control Rate (DCR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
The DCR was defined as the percentage of patients who achieved a best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study.
8 secondary outcomes
Plasma Concentrations of Surufatinib
Time frame: Cohorts A, B and C: Pre-dose and 1, 2, 3, 4 hours post-dose on Cycle 1 Day 15; Cohort D: Pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8 and 10 hours post-dose on Cycle 1 Day 15
Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment
Time frame: From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
Objective Response Rate (ORR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Time to Response (TTR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Duration of Response (DOR)
Time frame: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Progression-Free Survival (PFS)
Time frame: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline
Time frame: Baseline (Day -2) and Cycle 1 Day 15
Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Neuroendocrine Tumours
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Schelman, MD, PhD study director
Hutchmed
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Surufatinib in people with Neuroendocrine Tumours and Neuroendocrine Tumour of the Lung, run by Hutchmed at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Spain, Italy, Germany, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Control Rate (DCR) (time frame: RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025.