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Phase III Study of Sulfatinib in Treating Advanced Pancreatic Neuroendocrine Tumors

This study is currently recruiting participants.
Verified June 2017 by Hutchison Medipharma Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT02589821
First Posted: October 28, 2015
Last Update Posted: June 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Hutchison Medipharma Limited
  Purpose
A randomized, double-blind, placebo controlled, multi-center Phase III study to assess the efficacy of Sulfatinib 300 mg once a day in treating advanced pancreatic neuroendocrine tumors.

Condition Intervention Phase
Neuroendocrine Tumors Drug: Sulfatinib Other: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Multi-center Phase III Clinical Study to Assess the Efficacy and Safety of Sulfatinib Compared to Placebo in Patients With Advanced Pancreatic Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by Hutchison Medipharma Limited:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 7 months after the last patient enrolled ]
    the duration between the randomization date and the first disease progression (PD) or death (whichever comes first).


Secondary Outcome Measures:
  • The objective response rate of the tumor (ORR) [ Time Frame: 7 months after the last patient enrolled ]
    the incidence of confirmed complete response or partial response

  • The disease control rate (DCR) [ Time Frame: 7 months after the last patient enrolled ]
    the incidence of complete response, partial response and stable disease

  • Duration of Response (DoR) [ Time Frame: 7 months after the last patient enrolled ]
    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

  • Time to Response (TTR) [ Time Frame: 7 months after the last patient enrolled ]
    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).

  • Overall survival (OS) [ Time Frame: 7 months after the last patient enrolled ]
    the time from the date of randomization to the date of death (all causes)

  • •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 ]
    The safety and tolerability of sulfatinib 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.


Estimated Enrollment: 195
Actual Study Start Date: December 7, 2015
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sulfatinib
Sulfatinib 300 mg, orally, once daily (QD)
Drug: Sulfatinib
Sulfatinib 300 mg once a day (QD) will be orally administrated on a 28-day cycle
Other Name: •HMPL-012
Placebo Comparator: Placebo
Placebo 300 mg, orally, once daily (QD)
Other: Placebo
Placebo 300 mg once a day (QD) will be orally administrated on a 28-day cycle

Detailed Description:

195 patients will be randomly assigned (in 2:1 ratio) to the Sulfatinib 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) pancreatic neuroendocrine tumors (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 received no more than two types of systemic anti-tumor therapy, including long-acting somatostatin analogs (SSAs), interferon,peptide receptor radionuclide therapy, mammalian target of rapamycin (mTOR) inhibitors or chemotherapy; 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
  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), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) levels ≤ 2.5 times the ULN; and who do have liver metastatic, with ALT, AST and ALP ≤ 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.

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, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms;
  3. Have received anti-vascular endothelial growth factor(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 exceed 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 Cytochrome P450 3A4 (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 (HCV) 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02589821


Contacts
Contact: Neo Li +86 21-2067 3222 Jingli@hmplglobal.com

Locations
China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100032
Contact: Chunmei Bai, Prof.       baichunmei1964@163.com   
Principal Investigator: Chunmei Bai, Prof.         
the 307 Hospital of People's Liberation Army Recruiting
Beijing, Beijing, China, 100071
Contact: Jianming XU, Prof.       jmxu2003@yahoo.com   
Principal Investigator: Jianming XU, Prof.         
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Jie Li, Prof.       xiaotong10241@sina.com   
Principal Investigator: Jie Li, Prof.         
China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Zhiwei Zhou, Prof.       zhouzhw@sysucc.org.cn   
Principal Investigator: Zhiwei Zhou, Prof.         
China, Sichuan
West China Hospital, Sichuan University Recruiting
Chengdu, Sichuan, China, 610047
Contact: Zhiping Li, Prof.       lizhiping620312@163.com   
Principal Investigator: Zhiping Li, Prof.         
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
Study Director: Charlie Qi, MD Hutchison Medi Pharma
  More Information

Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT02589821     History of Changes
Other Study ID Numbers: 2015-012-00CH3
First Submitted: October 26, 2015
First Posted: October 28, 2015
Last Update Posted: June 20, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Adenoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases