ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
ClinicalTrials.gov Identifier: NCT03251378
Recruitment Status : Recruiting
First Posted : August 16, 2017
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

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

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: Fruquintinib (HMPL-013) Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center, Open-Label, Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fruquintinib in Advanced Solid Tumors
Actual Study Start Date : November 10, 2017
Estimated Primary Completion Date : December 15, 2019
Estimated Study Completion Date : December 15, 2019

Arm Intervention/treatment
Experimental: 3 mg Safety Run-In
3 mg of Fruquintinib (HMPL-013), tablet taken daily, 3 weeks on, 1 week off
Drug: Fruquintinib (HMPL-013)
Fruquintinib is a small molecule tyrosine kinase inhibitor (TKI) with a novel chemical structure which belongs to the quinazoline class.

Experimental: 5 mg Safety Run-In
5 mg of Fruquintinib (HMPL-013), tablet taken daily, 3 weeks on, 1 week off
Drug: Fruquintinib (HMPL-013)
Fruquintinib is a small molecule tyrosine kinase inhibitor (TKI) with a novel chemical structure which belongs to the quinazoline class.

Experimental: Fruquintinib Expansion Phase
The 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.
Drug: Fruquintinib (HMPL-013)
Fruquintinib is a small molecule tyrosine kinase inhibitor (TKI) with a novel chemical structure which belongs to the quinazoline class.




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 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 :
  1. 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. ]
    The time to reach Cmax will be measured for each subject (Tmax).

  2. 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. ]
    The apparent clearance (CL/F) will be determined during the terminal phase according to CL/F/Ke, and the accumulation index based on AUC

  3. To identify the recommended study Phase II dose (RP2D). [ Time Frame: Up to 1 year. ]
    The Maximum Tolerated Dose will be identified from the Safety Run-In Phase of this Study (Arms 1 & 2)

  4. 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 ]
    Activity will be determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1



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 to 75 Years   (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. 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.

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): NCT03251378


Contacts
Contact: Nathan Lautermilch 609 216-0274 maria.karvois@quintilesims.com

Locations
United States, Florida
St. Joseph Heritage Healthcare Recruiting
Miami, Florida, United States, 33018
Contact: Dr. Stanton         
Sponsors and Collaborators
Hutchison Medipharma Limited

Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT03251378     History of Changes
Other Study ID Numbers: 2015-013-00US1
First Posted: August 16, 2017    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No