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A Multi-Center, Open-Label Study of Surufatinib (HMPL-012) in Patients With Advanced Solid Tumors

NCT02549937

Description:

Primary Objective Dose Escalation: To evaluate the safety and tolerability of surufatinib in patients with advanced solid tumors and to determine the maximum tolerable dose (MTD) or recommended phase II dose (RP2D). Primary Objective Dose Expansion: To evaluate the anticancer activity of surufatinib in patients with advanced Biliary Tract Cancer (BTC), patients with advanced pancreatic neuroendocrine tumors (pNETs), patients with locally advanced, unresectable, metastatic extra-pancreatic neuroendocrine tumors (EP-NETs), and patients with soft tissue sarcomas (STS) treated at a dose of 300 mg QD. Secondary Objective: To evaluate the pharmacokinetic profile of multiple dose surufatinib in patients with advanced solid tumors and to evaluate the anti cancer activity of surufatinib in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Multi-Center, Open-Label Study of Surufatinib (HMPL-012) in Patients With Advanced Solid Tumors
  • Official Title: A Multi-Center, Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Surufatinib (HMPL-012), Previously Named Sulfatinib in Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2015-012-00US1
  • NCT ID: NCT02549937

Conditions

  • Tumors

Interventions

DrugSynonymsArms
surufatinibHMPL-012, sulfatinibEscalation 100mg

Purpose

Primary Objective Dose Escalation: To evaluate the safety and tolerability of surufatinib in patients with advanced solid tumors and to determine the maximum tolerable dose (MTD) or recommended phase II dose (RP2D). Primary Objective Dose Expansion: To evaluate the anticancer activity of surufatinib in patients with advanced Biliary Tract Cancer (BTC), patients with advanced pancreatic neuroendocrine tumors (pNETs), patients with locally advanced, unresectable, metastatic extra-pancreatic neuroendocrine tumors (EP-NETs), and patients with soft tissue sarcomas (STS) treated at a dose of 300 mg QD. Secondary Objective: To evaluate the pharmacokinetic profile of multiple dose surufatinib in patients with advanced solid tumors and to evaluate the anti cancer activity of surufatinib in patients with advanced solid tumors.

Detailed Description

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

      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 35 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 surufatinib dose levels at 50,100, 200, 300
           and 400 mg/day.

      Expansion phase:

      Approximately 105 patients will be enrolled into one of four open-label treatment arms during
      this phase: at least 30 patients with advanced BTC that has progressed on standard first-line
      chemotherapy will be assigned to Arm A, at least 15 patients with advanced pNET that has
      progressed on either everolimus, sunitinib, or both will be assigned to Arm B, at least 15
      patients with advanced EP-NET that has progressed on everolimus will be assigned to Arm C,
      and at least 45 patients with Soft Tissue Sarcoma will be assigned to Arm D. Subjects
      enrolled in this phase are to be evaluated for the safety, tolerability and pharmacokinetic
      (PK) characteristics to confirm the selected surufatinib dose.

      Subjects will receive surufatinib 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.
    

Trial Arms

NameTypeDescriptionInterventions
Escalation 50 mgExperimentalEscalation cohort at 50 mg/day
  • surufatinib
Escalation 100mgExperimentalEscalation cohort at 100 mg/day
  • surufatinib
Escalation 200 mgExperimentalEscalation cohort at 200 mg/day
  • surufatinib
Escalation 300 mgExperimentalEscalation cohort at 300 mg/day
  • surufatinib
Escalation 400 mgExperimentalEscalation cohort at 400 mg/day
  • surufatinib
ExpansionExperimentalSubjects will receive RP2D surufatinib daily treatment continuously with every 28-day treatment cycle. Four expansion cohorts will enroll BTC, pNET, EP-NET, and STS patients, respectively.
  • surufatinib

Eligibility Criteria

        Key Inclusion Criteria:

          -  Fully understand the study and voluntarily sign the informed consent form;

          -  At least 18 years old;

          -  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; locally advanced or metastatic pNET that has progressed on
             everolimus, sunitinib or both; locally advanced or metastatic EP-NET that has
             progressed on everolimus; advanced STS that has progressed on at least one line of
             standard therapy or refused standard frontline cytotoxic chemotherapy during the
             expansion phase;

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

        Exclusion Criteria:

          -  Hypertension that is not controlled by antihypertension medication, defined as:
             systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;

          -  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;

          -  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;

          -  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%;

          -  Systemic anti-neoplastic therapies within 4 weeks prior to the initiation of
             investigational treatment, including chemotherapy, radical radiotherapy,
             hormonotherapy, biotherapy and immunotherapy;

          -  Palliative radiotherapy for bone metastasis/lesion within 2 weeks;

          -  Known Human immunodeficiency virus (HIV) infection;

          -  Known clinically significant history of liver disease, including viral or other
             hepatitis, current alcohol abuse, or cirrhosis;

          -  Women who are pregnant or lactating;

          -  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;

          -  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;

          -  Received investigational treatment in another clinical study within 4 weeks prior to
             the initiation of investigational treatment;

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLT
Time Frame:From date of enrollment through end of Cycle 1, up to 28 days
Safety Issue:
Description:The primary outcome during dose escalation will be the incidence rate of DLTs

Secondary Outcome Measures

Measure:maximum plasma concentration calculated with Blood samples
Time Frame:within 30 days after the first dose
Safety Issue:
Description:Blood samples will be taken to measure the levels of study drug.
Measure:time to reach maximum concentration calculated with Blood samples
Time Frame:within 30 days after the first dose
Safety Issue:
Description:Blood samples will be taken to measure the levels of study drug
Measure:Objective response rate
Time Frame:within 30 days after the last dose
Safety Issue:
Description:the proportion of subjects who have a Complete Response or Partial Response

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hutchison Medipharma Limited

Trial Keywords

  • biliary
  • pancreatic
  • neuroendocrine
  • carcinoid
  • PNET
  • EP-NET
  • extrapancreatic
  • sarcoma
  • soft tissue sarcoma
  • STS
  • BTC

Last Updated

October 29, 2019