Neuroendocrine Tumor Grade 3Phase 2NCT05627427
Multi-cohort Study of Surufatinib Plus Sintilimab in Metastatic NEN and Pancreatic Carcinoma Who Failed Standard Chemotherapy
A Phase 2 study testing Surufatinib and Sintilimab in people with Neuroendocrine Tumor Grade 3 and Neuroendocrine Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial summary
Neuroendocrine neoplams (NENs) are uncommon, but with a significant increasing incidence and prevalence with advances in diagnostic techniques. NENs can originate from various parts of the body and are highly heterogeneous. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neuroendocrine Tumor Grade 3, Neuroendocrine Carcinoma, Pancreatic Carcinoma
- What is being tested?
- Surufatinib and Sintilimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2022to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-75 years;
- Histologically or cytologically confirmed metastatic advanced neuroendocrine tumor grade 3 (NET G3), neuroendocrine carcinoma (NEC), or pancreatic cancer;
- Previous failure of first-line standard treatment (radiologically confirmed disease progression or intolerable toxic side effects); patients receiving adjuvant therapy, disease recurrence during treatment or within 6 months after the last treatment is considered first-line treatment failure; (NEC cohort, NET G3 cohort)
- Previous failure of standard treatment (radiologically confirmed disease progression or intolerable toxic side effects); patients receiving adjuvant therapy, disease recurrence during treatment or within 6 months after the last treatment is considered first-line treatment failure; (Pancreatic cancer cohort)
- Measurable lesions that meet the requirements of RECIST (1.1); if the lesion that has previously received local therapy (radiotherapy, ablation, vascular intervention, etc.) is the only lesion, there must be a clear imaging basis for the disease progression of the lesion;
- Liver function Child-Pugh class A (5-6 points) or better class B (≤ 7 points) (see Appendix 3);
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- ECOG score of 0 or 1 (see Appendix 1);
- Expected survival ≥ 12 weeks;
- At least one measurable lesion (RECIST 1.1 criteria, see Appendix 2);
- Essentially normal function of major organs and bone marrow:
- Blood routine: WBC ≥ 4.0 x 109/L, neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 90 g/L; B) International normalized ratio (INR) ≤ 1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; C) Liver function: total bilirubin ≤ 1.5 x ULN; ALT/AST/ALP ≤ 2.5 x ULN in the absence of liver metastasis; ALT/AST/ALP ≤ 5 x ULN in the presence of liver metastasis; D) Renal function: serum creatinine ≤ 1.5 x ULN and creatinine clearance (CCr) 60 mL/min (see Appendix 6); E) Normal cardiac function, left ventricular ejection fraction (LVEF) ≥ 50% by two-dimensional echocardiography.
- Fully understand the study, voluntarily participate, and sign the informed consent form.
- Male or female patients of childbearing potential voluntarily use effective contraceptive methods during the study and within 6 months after the last study drug, such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered to be of childbearing potential unless they are naturally postmenopausal, have undergone artificial menopause, or have undergone sterilization (eg, hysterectomy, bilateral adnexectomy, or radiation ovarian irradiation).
Who cannot join
- Having received approved or investigational systemic anti-tumor therapy within 4 weeks before enrollment, including photodynamic therapy, chemotherapy, radical radiotherapy, ablation, local radiotherapy (palliative radiotherapy for bone metastases is allowed to be completed at least 2 weeks before study drug treatment), biological immunotherapy, targeted therapy, etc.;
- Patients with untreated central nervous system metastases, previously treated with systemic, radical brain or meningeal metastases (radiotherapy or surgery), and those who have been confirmed to be stable by imaging for at least 1 month and have stopped systemic sex hormone therapy (dose > 10 mg/day prednisone or other effective hormones) for more than 2 weeks without clinical symptoms can be included
- Participated in other domestic unapproved or unmarketed drug clinical trials within 4 weeks before enrollment and received the corresponding investigational drug treatment;
- Having received any surgical or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before the start of enrollment;
- Clinically significant electrolyte abnormalities as judged by the investigator;
- Patients with current hypertension uncontrolled by drugs, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;
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- Patients currently have any disease or condition that affects drug absorption, or patients cannot take oral surufatinib;
- Patients with active gastric and duodenal ulcer, ulcerative colitis and other gastrointestinal diseases or unresected tumors have active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation as judged by the investigator;
- Patients with evidence or history of significant bleeding tendency within 3 months before enrollment (bleeding > 30 mL, hematemesis, melena, hematochezia), hemoptysis (> 5 mL of fresh blood within 4 weeks) or thromboembolic events (including stroke events and/or transient ischemic attack) within 12 months;
- significant clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within 6 months prior to enrollment; congestive heart failure New York Heart Association (NYHA) class > 2; ventricular arrhythmia requiring medical treatment; electrocardiogram (ECG) showed QTc interval ≥ 480 milliseconds;
- Patients with other malignant tumors within the past 5 years, except for basal cell or squamous cell carcinoma of the skin after radical resection, or cervical carcinoma in situ;
- Active or uncontrolled serious infection (≥ CTC AE grade 2 infection);
- Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must rule out active HBV infection, that is, HBV DNA positive (> 1 × 104 copies/mL or > 2000 IU/ml); known hepatitis C virus (HCV) infection and HCV RNA positive (> 1 × 103 copies/mL), or other hepatitis, cirrhosis];
- Unresolved toxicities above CTCAE grade 1 due to any prior anticancer therapy, excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2;
- Symptomatic peripheral neuropathy (CTCAE ≥ grade 2);
- pregnant (positive pregnancy test before medication) or lactating women;
- Any other disease, clinically significant metabolic abnormalities, physical examination abnormalities, or laboratory abnormalities that, in the judgment of the investigator, would reasonably suspect that the patient has a disease or condition that would make the use of the study drug inappropriate (eg, having seizures and requiring treatment), or would compromise the interpretation of the study results, or place the patient at high risk.
- Urine routine showed urine protein ≥ 2 + and, and 24-hour urine protein > 1.0g;
- Patients who have previously received anti-VEGF/VEGFR-targeted drugs and have disease progression during treatment;
- Taking drugs containing components of Hypericum perforatum within 3 weeks before enrollment, or taking other strong inducers or strong inhibitors of CYP3A4 within 2 weeks before enrollment;
- According to the investigator 's judgment, the patient has other factors that may affect the study results or result in forced halfway termination of this study, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring concomitant treatment, severe laboratory abnormalities, accompanied by family or social factors, which may affect the patient' s safety.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Rui Liu
Tianjin, Tianjin Municipality, 300000
Rui Liu, 13602139003, liurui9003@163.com
About this study
Official title: Multi-cohort, Open-label, Single-centered Study of Surufatinib in Combination With Sintilimab in the Treatment of Metastatic Neuroendocrine Neoplasm and Pancreatic Carcinoma Who Failed Standard Chemotherapy
Neuroendocrine neoplams (NENs) are uncommon, but with a significant increasing incidence and prevalence with advances in diagnostic techniques. NENs can originate from various parts of the body and are highly heterogeneous. Neuroendocrine tumors (NET), dividing into G1, G2, G3, are well-differentiated types with slow growth and neuroendocrine carcinoma (NEC) are poorly-differentiated with high malignancy. Pancreatic carcinoma is one of the malignant neoplasms with a very high mortality rate.
For NET G3, NEC and pancreatic, there are limited treatment options especially for those who progressed on standard chemotherapy.
Read more
Surufatinib is a novel multi-targeted kinase inhibitor on VEGFR-1, 2, 3, FGFR1, and CSF1R, which has required the China NMPA approval on unresectable NETs (G1\&G2). The pivital phase III clinical trial on NEC is ongoing.
Sintilimab is a PD-1 inhibitor with the approval on gastric cancer, non-small cell lung cancer, hepatocellular carcinoma and Hodgkin lymphoma.
Clinical evidence has shown the anti-tumor activity of surufatinib in combination with PD-1 inhibitor in solid tumors, including NEN, small-cell lung cancer, G/GEJ cancer, etc.
The current study is to investigate the safety and efficacy of surufatinib in combination with sintilimab in the treatment of NET G3, NEC and pancreatic carcinoma, in order to provide more treatment options for the patients who failed standard chemotherapy.
- Being tested
- Surufatinib, Sintilimab
- Medical subject headings
- Carcinoma, Neuroendocrine, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurufatinibDrug
Also called HMPL-012
250mg, p.o., qd, q3w, until disease progression or other treatment termination criteria
SintilimabDrug
200mg, IV, D1, q3w, until disease progression or other treatment termination criteria
| Study group | Role | What they receive |
|---|---|---|
| Surufatinib in combination of Sintilimab | Experimental | Surufatinib Sintinlimab Receives: Drug: Surufatinib; Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) (RECIST1.1)
A duration from the date of initial treatment to disease progression or death of any cause.
Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 2 years
Secondary outcomes (4)
Overall Survival (OS)
Duration from the date of initial treatment to the date of death due to any cause
Measured: From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years)
Objective response rate (ORR)(RECIST1.1)
The incidence of confirmed complete response or partial response
Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy(up to approximately 2 years)
Disease control rate (DCR)(RECIST1.1)
Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.
Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)
TEAE rates
- evaluate number of patients with treatment-emergent adverse events as assessed
Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2022
- Study start1 Jul 2022
- Primary completion1 Apr 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine Tumor Grade 3Studies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe 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
- Model description
- Three cohorts.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rui Liu, Principal investigator, Tianjin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05627427
- Sponsor's protocol ID
- TJGI-004
- Status last verified
- Nov 2022
- First submitted
- 15 Nov 2022
- Last updated
- 25 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ji Z, Wang X, Ma L, Xin J, Wang Y, Liu S, Liu R. Efficacy and safety of surufatinib and sintilimab with or without chemotherapy for advanced high-grade neuroendocrine neoplasms and pancreatic cancer. NPJ Precis Oncol. 2026 May 13;10(1):288. doi: 10.1038/s41698-026-01478-y.
PubMed 42129445
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-cohort, Open-label, Single-centered Study of Surufatinib in Combination With Sintilimab in the Treatment of Metastatic Neuroendocrine Neoplasm and Pancreatic Carcinoma Who Failed Standard Chemotherapy
- ClinicalTrials.gov ID
- NCT05627427
- Acronym / sponsor ID
- TJGI-004
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 25 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neuroendocrine neoplams (NENs) are uncommon, but with a significant increasing incidence and prevalence with advances in diagnostic techniques. NENs can originate from various parts of the body and are highly heterogeneous. Neuroendocrine tumors (NET), dividing into G1, G2, G3, are well-differentiated types with slow growth and neuroendocrine carcinoma (NEC) are poorly-differentiated with high malignancy. Pancreatic carcinoma is one of the malignant neoplasms with a very high mortality rate.
For NET G3, NEC and pancreatic, there are limited treatment options especially for those who progressed on standard chemotherapy.
Surufatinib is a novel multi-targeted kinase inhibitor on VEGFR-1, 2, 3, FGFR1, and CSF1R, which has required the China NMPA approval on unresectable NETs (G1\&G2). The pivital phase III clinical trial on NEC is ongoing.
Sintilimab is a PD-1 inhibitor with the approval on gastric cancer, non-small cell lung cancer, hepatocellular carcinoma and Hodgkin lymphoma.
Clinical evidence has shown the anti-tumor activity of surufatinib in combination with PD-1 inhibitor in solid tumors, including NEN, small-cell lung cancer, G/GEJ cancer, etc.
The current study is to investigate the safety and efficacy of surufatinib in combination with sintilimab in the treatment of NET G3, NEC and pancreatic carcinoma, in order to provide more treatment options for the patients who failed standard chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Three cohorts.
| Arm | Type | Receives |
|---|---|---|
| Surufatinib in combination of Sintilimab | Experimental | Drug: Surufatinib, Drug: SintilimabSurufatinib Sintinlimab |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Aged 18-75 years;
- Histologically or cytologically confirmed metastatic advanced neuroendocrine tumor grade 3 (NET G3), neuroendocrine carcinoma (NEC), or pancreatic cancer;
- Previous failure of first-line standard treatment (radiologically confirmed disease progression or intolerable toxic side effects); patients receiving adjuvant therapy, disease recurrence during treatment or within 6 months after the last treatment is considered first-line treatment failure; (NEC cohort, NET G3 cohort)
- Previous failure of standard treatment (radiologically confirmed disease progression or intolerable toxic side effects); patients receiving adjuvant therapy, disease recurrence during treatment or within 6 months after the last treatment is considered first-line treatment failure; (Pancreatic cancer cohort)
- Measurable lesions that meet the requirements of RECIST (1.1); if the lesion that has previously received local therapy (radiotherapy, ablation, vascular intervention, etc.) is the only lesion, there must be a clear imaging basis for the disease progression of the lesion;
Key exclusion criteria (21 listed)
- Having received approved or investigational systemic anti-tumor therapy within 4 weeks before enrollment, including photodynamic therapy, chemotherapy, radical radiotherapy, ablation, local radiotherapy (palliative radiotherapy for bone metastases is allowed to be completed at least 2 weeks before study drug treatment), biological immunotherapy, targeted therapy, etc.;
- Patients with untreated central nervous system metastases, previously treated with systemic, radical brain or meningeal metastases (radiotherapy or surgery), and those who have been confirmed to be stable by imaging for at least 1 month and have stopped systemic sex hormone therapy (dose > 10 mg/day prednisone or other effective hormones) for more than 2 weeks without clinical symptoms can be included
- Participated in other domestic unapproved or unmarketed drug clinical trials within 4 weeks before enrollment and received the corresponding investigational drug treatment;
- Having received any surgical or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before the start of enrollment;
- Clinically significant electrolyte abnormalities as judged by the investigator;
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-012250mg, p.o., qd, q3w, until disease progression or other treatment termination criteria | Drug | Surufatinib in combination of Sintilimab |
| Sintilimab200mg, IV, D1, q3w, until disease progression or other treatment termination criteria | Drug | Surufatinib in combination of Sintilimab |
Primary outcome
Progression-free Survival (PFS) (RECIST1.1)
Time frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 2 years
A duration from the date of initial treatment to disease progression or death of any cause.
4 secondary outcomes
Overall Survival (OS)
Time frame: From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years)
Objective response rate (ORR)(RECIST1.1)
Time frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy(up to approximately 2 years)
Disease control rate (DCR)(RECIST1.1)
Time frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)
TEAE rates
Time frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2022.
- Derived from this study: PubMed 42129445Ji Z, Wang X, Ma L, Xin J, Wang Y, Liu S, Liu R. Efficacy and safety of surufatinib and sintilimab with or without chemotherapy for advanced high-grade neuroendocrine neoplasms and pancreatic cancer. NPJ Precis Oncol. 2026 May 13;10(1):288. doi: 10.1038/s41698-026-01478-y.
- Individual participant dataSharing planned: No
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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.
Rui Liu principal investigator
Tianjin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Surufatinib and Sintilimab in people with Neuroendocrine Tumor Grade 3 and Neuroendocrine Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
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 13 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 25 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rui Liu (13602139003, liurui9003@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (RECIST1.1) (time frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anticancer therapy (up to approximately 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05627427, which also lists 1 linked publication.
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 Nov 2022.