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Trial record 1 of 1 for:    NCT02549937
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A Multi-Center, Open-Label Study of Sulfatinib(HMPL-012) in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02549937
Recruitment Status : Recruiting
First Posted : September 15, 2015
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Brief Summary:

Primary Objective:

To evaluate the safety and tolerability of sulfatinib in patients with advanced solid tumors and to determine the maximum tolerable dose (MTD) or recommended phase II dose (RP2D).

Secondary Objective: To evaluate the pharmacokinetic profile of multiple dose sulfatinib in patients with advanced solid tumors and to evaluate the anti cancer activity of sulfatinib in patients with advanced solid tumors.


Condition or disease Intervention/treatment Phase
Tumors Drug: sulfatinib Phase 1

Detailed Description:

The study is an open-label, dose escalation clinical trial of sulfatinib orally once daily (QD) in patients with advanced solid tumor.

The study consists of two phases:

Dose escalation phase - A 3+3 design will be used for this portion of the study.

  • Approximately 15 to 30 evaluable patients will be enrolled. The actual number of patients depends on the Dose-limiting toxicity (DLT) situation as well as the RP2D dose level reached in this trial.
  • The trial will approximately evaluate five sulfatinib dose levels at 50,100, 200, 300 and 400 mg/day.

Expansion phase:

The expansion phase will confirm the MTD with an additional 6 patients enrolled in the 400 mg/day escalation cohort. In consultation with the study investigators, observed toxicities, tolerability, and drug exposure will be evaluated.

Approximately 30 patients will be enrolled into one of two open-label treatment arms during this phase: at least 15 patients with advanced BTC that has progressed on standard first-line chemotherapy will be assigned to Arm A, and at least 15 patients with advanced pNET that has progressed on either everolimus, sunitinib, or both will be assigned to Arm B. Subjects enrolled in this phase are to be evaluated for the safety, tolerability and pharmacokinetic (PK) characteristics to confirm the selected sulfatinib dose.

Subjects will receive sulfatinib daily treatment continuously with every 28-day treatment cycle until disease progression, death, or intolerable toxicity at the investigator's discretion for a favorable benefit to risk balance.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics of Sulfatinib in Advanced Solid Tumors
Actual Study Start Date : November 2015
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

Arm Intervention/treatment
Experimental: Sulfatinib
Dose escalation phase:five sulfatinib dose levels at 50,100, 200, 300 and 400 mg/day will be dosed; Expansion phase: Subjects will receive RP2D sulfatinib daily treatment continuously with every 28-day treatment cycle.
Drug: sulfatinib
orally once daily (QD) in patients with advanced solid tumor.
Other Name: HMPL-012




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. maximum plasma concentration calculated with Blood samples [ Time Frame: within 30 days after the first dose ]
    Blood samples will be taken to measure the levels of study drug.

  2. time to reach maximum concentration calculated with Blood samples [ Time Frame: within 30 days after the first dose ]
    Blood samples will be taken to measure the levels of study drug

  3. Objective response rate [ Time Frame: within 30 days after the last dose ]
    the proportion of subjects who have a Complete Response or Partial Response



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Fully understand the study and voluntarily sign the informed consent form;
  2. At least 18 years old;
  3. 3. Histologically or cytologically documented, locally advanced or metastatic solid malignancy of any type during the dose escalation phase, that has progressed on available standard systemic therapy, and for whom no effective therapy or standard of care exists; and locally advanced or metastatic BTC that has progressed on standard first-line chemotherapy, and locally advanced or metastatic pNET that has progressed on everolimus, sunitinib or both, during the expansion phase;
  4. Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors Version (RECIST)1.1
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Expected survival of more than 12 weeks;
  7. Male or female patients of child-producing potential must agree to use two methods of the following contraceptive: condoms,intrauterine device (IUD), contraceptives (oral or parenteral), Implanon, injectables during the study and up to 90 days post the last day of study treatment.

Exclusion Criteria:

  1. Absolute neutrophil count (ANC) of < 1.5×109/L, or platelet count of < 100 ×109/L, or hemoglobin < 9g/dL;
  2. Serum total bilirubin > 1.5 times the upper limit of normal (ULN);
  3. Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) or alkaline phosphatase (ALP) > 2.5 ULN without hepatic metastases or ALT, AST or ALP > 5 ULN with hepatic metastases
  4. Clinically significant abnormal serum potassium (regardless of potassium agent supplementation); serum calcium (ionic or binding to albumin post-adjusted) or serum magnesium (regardless of magnesium agent supplementation);
  5. Serum creatinine clearance < 60 ml/min on the basis of either 24-hour urine collection or the glomerate filtration rate estimated by Cockraft-Gault equation
  6. Urine protein > 2+; Patients discovered to have ≥ 1+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24-hour urine;
  7. Uncontrolled hypertension, defined as: systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;
  8. International Normalized Ratio (INR) > 1.5 ULN or activated partial thromboplastin time (aPTT) > 1.5 ULN. Subject is currently receiving or intending to receive anti-coagulants for therapeutic purposes. Prophylactic use of anticoagulants is allowed.
  9. History or presence of digestive tract diseases, including active gastric/duodenal ulcer or ulcerative colitis, or active hemorrhage of an unresected gastrointestinal tumor, or an evaluation by investigators of having any other condition that could possibly result in gastrointestinal tract hemorrhage or perforation;
  10. History or presence of serious hemorrhage , hemoptysis or hematemesis within 3 months or a thromboembolic event (including Deep Vein Thrombosis (DVT), stroke and/or transient ischemic attack) within 6 months; Patients with squamous Non Small Cell Lung Cancer (NSCLC) should be excluded.
  11. 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, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment or left ventricular ejection fraction (LVEF) < 50%;
  12. Mean corrected QT interval (QTc) > 480 msec or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in a next-of-kin relative.
  13. Currently use medications known to cause QT prolongation or Torsades de Pointes.
  14. Systemic anti-neoplastic therapies within 4 weeks prior to the initiation of investigational treatment, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and immunotherapy;
  15. Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of study treatment;
  16. Strong inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John‟s Wort).
  17. Surgery prior to enrollment within 28 days prior to the initiation of study treatment or unhealed surgical incision;
  18. Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for alopecia);
  19. Known Human immunodeficiency virus (HIV) infection;
  20. Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  21. Evidence of ongoing or active infection requiring intravenous antibiotics;
  22. Women who are pregnant or lactating;
  23. Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease for 14 days or longer; Subjects requiring steroids within 4 weeks prior to start of study treatment will be excluded;
  24. Inability to take medication orally, dysphagia or an active gastric ulcer resulting from previous surgery or a severe gastrointestinal disease,or any other condition that investigators believe may affect absorption of the investigational product;
  25. Received investigational treatment in another clinical study within 4 weeks prior to the initiation of investigational treatment;
  26. Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition that investigators suspect may prohibit use of the investigational product, affect interpretation of study results, or put the patient at high risk.

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): NCT02549937


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

Locations
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United States, Colorado
SCRI at HealthONE Recruiting
Denver, Colorado, United States, 80218
Contact: Gerald Falchook, Dr.    720-754-2610    Gerald.Falchook@scresearch.net   
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Judy Wang, Dr.    239-349-8989    jswang@flcancer.com   
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Erika Hamilton, Dr.    615-329-7274    ehamilton@tnonc.com   
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: Charlie Qi, MD Hutchison Medi Pharma

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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT02549937     History of Changes
Other Study ID Numbers: 2015-012-00US1
First Posted: September 15, 2015    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided