Clinical Trials /

Phase III Study of Surufatinib in Treating Advanced Pancreatic Neuroendocrine Tumors

NCT02589821

Description:

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 pancreatic neuroendocrine tumors.

Related Conditions:
  • Pancreatic Neuroendocrine Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase III Study of Surufatinib in Treating Advanced Pancreatic Neuroendocrine Tumors
  • Official Title: A Randomized, Double-blind, Multi-center Phase III Clinical Study to Assess the Efficacy and Safety of Surufatinib Compared to Placebo in Patients With Advanced Pancreatic Neuroendocrine Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2015-012-00CH3
  • NCT ID: NCT02589821

Conditions

  • Neuroendocrine Tumors

Interventions

DrugSynonymsArms
SurufatinibHMPL-012, SulfatinbSurufatinib

Purpose

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 pancreatic neuroendocrine tumors.

Detailed Description

      195 patients will be randomly assigned (in 2:1 ratio) to the Surufatinib or Placebo treatment
      group based on interactive web response system(IWRS).The patients will receive continuous
      oral treatment, every 28-day treatment cycle until progression of disease occurs, intolerable
      toxicity or other protocol specified end-o-treatment criteria is met. The tumor should be
      assessed every 8 weeks (+/-3 days) within the first year and every 12 weeks (+/-3 days) after
      the patient has been treated for one year.

      A Blinded Independent Image Review Committee (BIIRC) will subsequently provide a central
      review of the oncologic imaging materials from the patients.

      An independent Data Monitoring Committee (IDMC) will be assembled to monitor safety and
      efficacy data, and evaluate interim analysis. If the interim analysis demonstrates
      overwhelming efficacy of the treatment arm with respect to PFS (primary endpoint) versus
      control arm, IDMC could recommend terminating and to unblinding the study and sulfatinib will
      be offered to the control arm patients who are still on treatment until disease progression
      or intolerable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
SurufatinibExperimentalSurufatinib 300 mg, orally, once daily (QD)
  • Surufatinib
PlaceboPlacebo ComparatorPlacebo 300 mg, orally, once daily (QD)

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Adequately understand the study and voluntarily sign the Informed Consent Form;
    
              2. Be at least 18 years old;
    
              3. 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) PNET. 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. If the mitotic
                 ratio and Ki-67 index correspond to different grade, the higher grade should be used
                 to assign classification.
    
              4. 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;
    
              5. Patients must have radiological documentation of progression of disease within 12
                 months prior to randomization.
    
              6. Have measurable lesions (according to RECIST 1.1);
    
              7. Absolute neutrophil count (ANC) of ≥1.5×109/L, platelet count of ≥100×109/L, and
                 hemoglobin ≥9 g/dL;
    
              8. Serum total bilirubin <1.5 times the upper limit of normal (ULN);
    
              9. 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
                 metastatic, with ALT and AST ≤ 5 times ULN.
    
             10. Serum creatinine <1.5 times ULN and creatinine clearance ≥60 ml/min;
    
             11. International Normalized Ratio (INR) ≤1.5 ULN and activated partial thromboplastin
                 time (APTT) ≤1.5 ULN.
    
             12. Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group
                 (ECOG) scale;
    
             13. Have expected survival of more than 12 weeks;
    
             14. 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).
    
            Exclusion Criteria:
    
              1. High grade (G3) neuroendocrine cancer, adenocarcinoid, pancreatic islet cell
                 carcinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell
                 carcinoma;
    
              2. 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;
    
              3. Have received anti-VEGF/VEGFR targeted drugs and progressed upon these drugs;
    
              4. Urinalysis shows urine protein ≥ 2+ or 24-hour protein quantity test shows urinary
                 protein ≥1 g;
    
              5. Serum potassium, calcium (albumin-bound ionic or corrected) or magnesium exceeds the
                 normal range with clinical significance;
    
              6. Under anti-hypertension treatment, still uncontrolled hypertension, defined as:
                 systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg;
    
              7. 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;
    
              8. 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;
    
              9. 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%;
    
             10. Mean corrected QT interval (QTc) ≥ 480 msec;
    
             11. Other malignancies diagnosed within the previous 5 years, except basal cell carcinoma
                 or cervical carcinoma in situ after radical resection;
    
             12. 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 ;
    
             13. Palliative radiotherapy for a bone metastasis lesion within 2 weeks prior to the
                 initiation of the investigational treatment;
    
             14. 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);
    
             15. Any clinically significant active infection, including, but not limited to, human
                 immunodeficiency virus (HIV) infection;
    
             16. History of clinically significant hepatic disease, including, but not limited to,
                 known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×104/ml);
                 known Hepatitis C virus infection with HCV RNA positive (copies ≥1×103/m); or liver
                 cirrhosis, etc.
    
             17. Surgery (except biopsy) within 28 days prior to the initiation of investigational
                 treatment or unhealed surgical incision; 18 Brain metastases and/or spinal cord
                 compression not treated by surgery and/or radiotherapy, and with no clinical imaging
                 evidence of disease stability;
    
            19. Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1
            (except for hair loss); 20. Received investigational treatments in other clinical studies
            within 4 weeks prior to enrollment; 21. Women who are pregnant or lactating; 22. Other
            disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or
            any other conditions are inappropriate for the use of the investigational product or affect
            interpretation of study results.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression Free Survival (PFS)
    Time Frame:7 months after the last patient enrolled
    Safety Issue:
    Description:the duration between the randomization date and the first disease progression (PD) or death (whichever comes first).

    Secondary Outcome Measures

    Measure:The objective response rate of the tumor (ORR)
    Time Frame:7 months after the last patient enrolled
    Safety Issue:
    Description:the incidence of confirmed complete response or partial response
    Measure:The disease control rate (DCR)
    Time Frame:7 months after the last patient enrolled
    Safety Issue:
    Description:the incidence of complete response, partial response and stable disease
    Measure:Duration of Response (DoR)
    Time Frame:7 months after the last patient enrolled
    Safety Issue:
    Description:the duration between the date the criteria for complete response or partial response was first measured (first record shall prevail) and the date of disease recurrence or progression as objectively recorded
    Measure:Time to Response (TTR)
    Time Frame:7 months after the last patient enrolled
    Safety Issue:
    Description:the period from the date of randomization to the date when the criteria for complete response or partial response was first measured (first record shall prevail).
    Measure:Overall survival (OS)
    Time Frame:7 months after the last patient enrolled
    Safety Issue:
    Description:the time from the date of randomization to the date of death (all causes)
    Measure:•adverse events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
    Time Frame:From first dose to within 30 days after the last dose
    Safety Issue:
    Description:The safety and tolerability of Surufatinib will be evaluated based on adverse events data. Other safety parameters include physical examination, vital signs, laboratory test results (i.e., hematology, chemistry panel, and urinalysis), 12-lead electrocardiogram, and ultrasonic cardiogram.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Hutchison Medipharma Limited

    Last Updated

    November 18, 2019