Clinical Trials /

Phase I Evaluation of Safety, Tolerability, and Pharmacokinetics for Fruquintinib in Solid Tumors

NCT03251378

Description:

An open-label, dose escalation and expansion clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors and metastatic colorectal cancer.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: The Evaluation of Safety, Tolerability, and Pharmacokinetics for Fruquintinib in Solid Tumors
  • Official Title: A Multi-Center, Open-Label, Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fruquintinib in Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 2015-013-00US1
  • NCT ID: NCT03251378

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
Fruquintinib (HMPL-013)3 mg Safety Run-In

Purpose

An open-label, dose escalation clinical trial to evaluate the safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors.

Detailed Description

      The study is an open-label, dose escalation clinical trial to evaluate the safety,
      tolerability, and PK of fruquintinib in patients with advanced solid tumors. Study will be
      conducted in up to 5 sites in the US.
    

Trial Arms

NameTypeDescriptionInterventions
3 mg Safety Run-InExperimental3 mg of Fruquintinib (HMPL-013), tablet taken daily, 3 weeks on, 1 week off
  • Fruquintinib (HMPL-013)
5 mg Safety Run-InExperimental5 mg of Fruquintinib (HMPL-013), tablet taken daily, 3 weeks on, 1 week off
  • Fruquintinib (HMPL-013)
Fruquintinib Expansion PhaseExperimentalThe fruquintinib dose as the recommended tolerated dose from the safety run-in arms. Dose: Fruquintinib (HMPL-013), (dose to be determined) mg, tablet taken daily, 3 weeks on, 1 week off.
  • Fruquintinib (HMPL-013)

Eligibility Criteria

        Inclusion Criteria:

          1. Fully understand the study and voluntarily sign the informed consent form;

          2. 18-75 years of age

          3. Body weight ≥ 45kg

          4. Histologically or cytologically documented, locally advanced or metastatic solid
             malignancy (except squamous NSCLC) that has progressed on approved systemic therapy,
             the last dose of prior systemic anti-cancer therapy must have been administered ≥ 4
             weeks prior to initiation of study treatment, and for whom no effective therapy or
             standard of care exists.

          5. Have measurable disease per RECIST Version 1.1 (expansion phase only)

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

          7. Expected survival of more than 12 weeks;

          8. For female patients of childbearing potential and male patients with partners of
             childbearing potential, agreement (by patient and partner) to use a highly effective
             form(s) of contraception that results in a low failure rate ( < 1% per year) when used
             consistently and correctly, and to continue its use for 90 days after the last dose of
             fruquintinib.

        Exclusion Criteria:

        Patients will be excluded from the study, if any of the following criteria is met:

          1. Absolute neutrophil count (ANC) < 1.5×109/L, platelet count < 100 ×109/L, or
             hemoglobin < 90 g/L;

          2. Serum total bilirubin > 1.5 times the upper limit of normal (ULN);

          3. Alanine aminotransferase (ALT) aspartate aminotransferase (AST) > 1.5 ULN in patients
             without hepatic metastases or ALT, AST > 3 ULN in patients with hepatic metastases;

          4. Serum potassium, calcium, or magnesium levels out of the normal laboratory reference
             range, and clinically significant in the investigator's judgment.

          5. Serum creatinine clearance < 60 mL/min;

          6. Urine dipstick for proteinuria > 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 hours;

          7. Uncontrolled hypertension, defined as: systolic blood pressure ≥ 140 mmHg and/or
             diastolic blood pressure ≥ 90mmHg;

          8. International Normalized Ratio (INR) > 2 or activated partial thromboplastin time
             (aPTT) > 1.5 ULN, except if the patient is currently receiving or intending to receive
             anti-coagulants for therapeutic purposes (prophylactic use is allowed).

          9. Risk of, or active hemorrhage: history or presence of active gastric/duodenal ulcer or
             ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, or any
             other condition that could possibly result in gastrointestinal tract hemorrhage or
             perforation;

         10. History or presence of hemorrhage from any other site (e.g., hemoptysis or
             hematemesis) within 2 months prior to screening

         11. History of a thromboembolic event (including DVT, pulmonary embolism, stroke and/or
             transient ischemic attack) within 12 months prior to screening;

         12. Patients with squamous non-small-cell lung cancer (NSCLC);

         13. Clinically significant cardiovascular disease, including but not limited to acute
             myocardial infarction or coronary artery bypass surgery within 6 months prior to
             enrollment, severe or unstable angina pectoris, New York Heart Association Class
             III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left
             ventricular ejection fraction (LVEF) < 50%;

         14. Mean corrected QT interval using the Fredericia method (QTcF) > 480 msec or any
             factors that increase the risk of QTc prolongation or risk of arrhythmic events such
             as hypokalemia, 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.

         15. Concomitant medications with a known risk of causing QT prolongation and/or Torsades
             de Pointes (See list in Appendix E; source list is continuously updated online at
             www.qtdrugs.org ).

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

         17. Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the
             initiation of study treatment;

         18. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of
             study treatment (3 weeks for St John's Wort). See Appendix F for a list of such
             medications.

         19. Surgery prior to enrollment within 28 days prior to the initiation of study treatment
             or unhealed surgical incision;

         20. Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1
             (except for alopecia);

         21. Known human immunodeficiency virus (HIV), hepatitis A, B or C infection except for
             fully recovered Hepatitis A. Previous medical history of hepatitis B virus (HBV)
             infection regardless of drug control, HBV DNA ≥104 ×copy number or ≥2000 IU/mL;

         22. Known clinically significant history of liver disease, including hepatitis or
             cirrhosis; current alcohol abuse.,

         23. Evidence of ongoing or active infection requiring intravenous antibiotics;

         24. Women who are pregnant or lactating;

         25. Central nervous system (CNS) metastatic disease or prior cerebral metastasis;

         26. Inability to take medication orally, dysphagia or an active gastric ulcer resulting
             from previous surgery (e.g., gastric bypass) or a severe gastrointestinal disease, or
             any other condition that investigators believe may affect absorption of the
             investigational product;

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

         28. 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
             undue risk of harm.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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 Fruquintinib 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

Measure:To measure the time to reach maximum plasma concentration of fruquintinib in patients with advanced solid tumors.
Time Frame:From Cycle 1, Day 1, 10 mins pre-dose 1st dose until Cycle 1, Day 22 10 mins pre-dose.
Safety Issue:
Description:The time to reach Cmax will be measured for each subject (Tmax).
Measure:To evaluate metabolite profile (in plasma) of fruquintinib in patients with advanced solid tumors
Time Frame:From Cycle 1, Day 1, 10 mins pre-dose 1st dose until Cycle 1, Day 22 10 mins pre-dose.
Safety Issue:
Description:The apparent clearance (CL/F) will be determined during the terminal phase according to CL/F/Ke, and the accumulation index based on AUC
Measure:To identify the recommended study Phase II dose (RP2D).
Time Frame:Up to 1 year.
Safety Issue:
Description:The Maximum Tolerated Dose will be identified from the Safety Run-In Phase of this Study (Arms 1 & 2)
Measure:To evaluate anticancer activity of fruquintinib in patients with advanced solid tumors.
Time Frame:From first dose to within 30 days after the last dose
Safety Issue:
Description:Activity will be determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Details

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

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