Phase III Study of Surufatinib in Treating Advanced Extrapancreatic Neuroendocrine Tumors

NCT02588170 | Completed Phase 3 DMC

• 1 other identifier: 2015-012-00CH4
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 5

Brief Summary

A randomized, double-blind, placebo controlled, multi-center Phase III study to assess the efficacy of Surufatinib 300 mg once a day in treating advanced extrapancreatic neuroendocrine tumors.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  the duration between the randomization date and the first disease progression (PD) or death (whichever comes first).

  9 months after the last patient enrolled

Secondary Outcomes (6)

• The objective response rate of the tumor (ORR)

  9 months after the last patient enrolled

• The disease control rate (DCR)

  9 months after the last patient enrolled

• Duration of Response (DoR)

  9 months after the last patient enrolled

• Time to Response (TTR)

  9 months after the last patient enrolled

• Overall survival

  9 months after the last patient enrolled

Study Arms (2)

Surufatinib

EXPERIMENTAL

Surufatinib 300 mg, orally, once daily (QD)

Drug: Surufatinib

Placebo

PLACEBO COMPARATOR

Placebo 300 mg, orally, once daily (QD)

Other: Placebo

Interventions

Surufatinib DRUG

Surufatinib 300 mg once a day (QD) will be orally administrated on a 28-day cycle

Also known as: HMPL-012, Sulfatinib

Surufatinib

Placebo OTHER

Placebo 300 mg once a day (QD) will be orally administrated on a 28-day cycle

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adequately understand the study and voluntarily sign the Informed Consent Form;
• Be at least 18 years old;
• Based on central pathology review results，patients have a confirmed histologically pathology diagnosis of low- or intermediate grade (G1 or G2) advanced (unresectable or distant metastatic) extrapancreatic NETs with origins including, but not limited to, the lung, thymus, the gastrointestinal tract (stomach, duodenum, liver, jejunum, ileum, colon, cecum, appendix, rectum) and unknown origin etc. For Gastrointestinal neuroendocrine tumors (GI-NETs), G1 is defined as \< 2 mitoses /10 high-power field［HPF］and/or \<3% Ki-67 index; G2 is defined as 2-20/10 HPF and/or 3-20% Ki-67 index; for NETs originating from the lung and thymus gland, G1 is defined as \<2 mitoses/10 HPF and no necrosis; G2 is defined as 2-10/10 HPF and/or foci of necrosis. NETs from origin other than GI-NET, lung and thymus, or from unknown origins should be graded according to the GI-NET grading criteria. If the mitotic ratio and Ki-67 index correspond to different grade, the higher grade should be used to assign classification.
• Have previously progressed on no more than two types of systemic anti-tumor therapy, including long-acting somatostatin analogs (SSAs), interferon, PRRT(peptide receptor radionuclide therapy), mTOR inhibitors or chemotherapy(chemotherapies were considered as one kind of regimen, regardless of medications and cycles); patients who are unable or unwilling to receive such treatments are also eligible;
• Patients must have radiological documentation of progression of disease within 12 months prior to randomization.
• Have measurable lesions (according to RECIST 1.1);
• Absolute neutrophil count (ANC) of ≥1.5×109/L, platelet count of ≥100×109/L, and hemoglobin ≥9 g/dL;
• Serum total bilirubin \<1.5 times the upper limit of normal (ULN);
• Patients who do not have liver metastasis, with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤ 2.5 times the ULN; and who do have liver metastasis, with ALT and AST ≤ 5 times ULN.
• Serum creatinine \<1.5 times ULN and creatinine clearance ≥60 ml/min;
• International Normalized Ratio (INR) ≤1.5 ULN and activated partial thromboplastin time (APTT) ≤1.5 ULN.
• Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale;
• Have expected survival of more than 12 weeks;
• Male or females patients with reproductive potential must agree to use an effective contraceptive method, for example, double-barrier device, condom, oral or injected birth control medication or intrauterine device, during the study and within 90 days after study treatment discontinuation. All female patients are considered to be fertile, unless the patient had natural menopause or artificial menopause or sterilization (such as hysterectomy, bilateral oophorectomy or ovarian irradiation).

You may not qualify if:

• High grade (G3) neuroendocrine cancer, adenocarcinoid, pancreatic islet cell carcinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma;
• Neuroendocrine tumors with pancreatic origins
• Functional NETs which need to be treated with long acting SSAs to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, ACTHoma, VIPoma, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms;
• Have received anti-VEGF/VEGFR targeted drugs and progressed upon these drugs;
• Urinalysis shows urine protein ≥ 2+ or 24-hour protein quantity test shows urinary protein ≥1 g;
• Serum potassium, calcium (albumin-bound ionic or corrected) or magnesium exceed the normal range with clinical significance;
• Under anti-hypertension treatment, still uncontrolled hypertension, defined as: systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg;
• Gastrointestinal disease or condition 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 may cause bleeding or perforation by investigator's discretion;
• History or presence of a serious hemorrhage (\>30 ml within 3 months), hemoptysis (\>5 ml blood within 4 weeks) or a thromboembolic event (including transient ischemic attack) within 12 months;
• Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification ≥ 2; ventricular arrhythmias which needs drug treatment; LVEF (LVEF) \<50%;
• Mean corrected QT interval (QTc) ≥ 480 msec;
• Other malignancies diagnosed within the previous 5 years, except basal cell carcinoma or cervical carcinoma in situ after radical resection;
• Anti-tumor therapy received within 4 weeks prior to the initiation of the investigational treatment, including, but not limited to, chemotherapy, radical radiotherapy, targeted therapy, immunotherapy and anti-tumor Chinese medicine treatment, hepatic chemoembolization, cryoablation and radiofrequency ablation ;
• Palliative radiotherapy for a bone metastasis lesion within 2 weeks prior to the initiation of the investigational treatment;
• Drugs containing St John's wort taken within 3 weeks prior to the first study treatment, or other strong inducers with CYP3A4 or strong inhibitors taken within two weeks prior to the first study treatment (see appendix 3);

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (5)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

the 307 Hospital of People's Liberation Army

Beijing, Beijing Municipality, 100071, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610047, China

Location

Related Publications (4)

• Xu J, Shen L, Li J, Zhou Z, Bai C, Li Z, Chi Y, Li E, Yu X, Xu N, Bai Y, Wang X, Yuan X, Liu T, Yin Y, Chen J, Hu H, Li X, Xiu D, Zhang T, Lou W, Ying J, Qin S, Deng Y, Tao M, Cheng Y, Fan S, Luo X, Guo X, Shi MM, Su W. Surufatinib in advanced neuroendocrine tumours: Final overall survival from two randomised, double-blind, placebo-controlled phase 3 studies (SANET-ep and SANET-p). Eur J Cancer. 2025 Jun 3;222:115398. doi: 10.1016/j.ejca.2025.115398. Epub 2025 Mar 30.

  PMID: 40306120 DERIVED

• Li J, Cheng Y, Bai C, Xu J, Shen L, Li J, Zhou Z, Li Z, Chi Y, Yu X, Li E, Xu N, Liu T, Lou W, Bai Y, Yuan X, Wang X, Yuan Y, Chen J, Guan S, Fan S, Su W. Health-related quality of life in patients with advanced well-differentiated pancreatic and extrapancreatic neuroendocrine tumors treated with surufatinib versus placebo: Results from two randomized, double-blind, phase III trials (SANET-p and SANET-ep). Eur J Cancer. 2022 Jul;169:1-9. doi: 10.1016/j.ejca.2022.03.027. Epub 2022 Apr 28.

  PMID: 35489301 DERIVED

• Li J, Cheng Y, Bai C, Xu J, Shen L, Li J, Zhou Z, Li Z, Chi Y, Yu X, Li E, Xu N, Liu T, Lou W, Bai Y, Yuan X, Wang X, Yuan Y, Chen J, Guan S, Fan S, Su W. Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies. ESMO Open. 2022 Apr;7(2):100453. doi: 10.1016/j.esmoop.2022.100453. Epub 2022 Mar 25.

  PMID: 35344750 DERIVED

• Xu J, Shen L, Zhou Z, Li J, Bai C, Chi Y, Li Z, Xu N, Li E, Liu T, Bai Y, Yuan Y, Li X, Wang X, Chen J, Ying J, Yu X, Qin S, Yuan X, Zhang T, Deng Y, Xiu D, Cheng Y, Tao M, Jia R, Wang W, Li J, Fan S, Peng M, Su W. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Nov;21(11):1500-1512. doi: 10.1016/S1470-2045(20)30496-4. Epub 2020 Sep 20.

  PMID: 32966811 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

surufatinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Songhua Fan, MD

  Hutchison Medi Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: October 27, 2015
• Study Start: December 7, 2015
• Primary Completion: March 31, 2019
• Study Completion: July 7, 2022
• Last Updated: March 30, 2023

Record last verified: 2023-03

Locations

CN (5)