Trial Title:
Multi-cohort Study of Surufatinib Plus Sintilimab in Metastatic NEN and Pancreatic Carcinoma Who Failed Standard Chemotherapy
NCT ID:
NCT05627427
Condition:
Neuroendocrine Tumor Grade 3
Neuroendocrine Carcinoma
Pancreatic Carcinoma
Conditions: Official terms:
Carcinoma
Neuroendocrine Tumors
Carcinoma, Neuroendocrine
Pancreatic Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Three cohorts.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Surufatinib
Description:
250mg, p.o., qd, q3w, until disease progression or other treatment termination criteria
Arm group label:
Surufatinib in combination of Sintilimab
Other name:
HMPL-012
Intervention type:
Drug
Intervention name:
Sintilimab
Description:
200mg, IV, D1, q3w, until disease progression or other treatment termination criteria
Arm group label:
Surufatinib in combination of Sintilimab
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. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged 18-75 years;
2. Histologically or cytologically confirmed metastatic advanced neuroendocrine tumor
grade 3 (NET G3), neuroendocrine carcinoma (NEC), or pancreatic cancer;
3. 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)
4. 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)
5. 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;
6. Liver function Child-Pugh class A (5-6 points) or better class B (≤ 7 points) (see
Appendix 3);
7. ECOG score of 0 or 1 (see Appendix 1);
8. Expected survival ≥ 12 weeks;
9. At least one measurable lesion (RECIST 1.1 criteria, see Appendix 2);
10. Essentially normal function of major organs and bone marrow:
A) 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.
11. Fully understand the study, voluntarily participate, and sign the informed consent
form.
12. 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).
Exclusion Criteria:
1. 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.;
2. 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
3. Participated in other domestic unapproved or unmarketed drug clinical trials within
4 weeks before enrollment and received the corresponding investigational drug
treatment;
4. Having received any surgical or invasive treatment or operation (except venous
catheterization, puncture and drainage, etc.) within 4 weeks before the start of
enrollment;
5. Clinically significant electrolyte abnormalities as judged by the investigator;
6. Patients with current hypertension uncontrolled by drugs, defined as systolic blood
pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;
7. Patients currently have any disease or condition that affects drug absorption, or
patients cannot take oral surufatinib;
8. 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;
9. 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;
10. 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;
11. 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;
12. Active or uncontrolled serious infection (≥ CTC AE grade 2 infection);
13. 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];
14. Unresolved toxicities above CTCAE grade 1 due to any prior anticancer therapy,
excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2;
15. Symptomatic peripheral neuropathy (CTCAE ≥ grade 2);
16. pregnant (positive pregnancy test before medication) or lactating women;
17. 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.
18. Urine routine showed urine protein ≥ 2 + and, and 24-hour urine protein > 1.0g;
19. Patients who have previously received anti-VEGF/VEGFR-targeted drugs and have
disease progression during treatment;
20. 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;
21. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Rui Liu
Address:
City:
Tianjin
Zip:
300000
Country:
China
Status:
Recruiting
Contact:
Last name:
Rui Liu
Phone:
13602139003
Email:
liurui9003@163.com
Start date:
July 1, 2022
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05627427
