A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Fruquintinib in Patients with Solid Tumors and Refractory Metastatic Colorectal Cancer

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria: 

  • Fully understand the study and voluntarily sign the informed consent form.
  • 18-75 years of age.
  • Body weight ≥ 45kg.
  • 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.
  • Have measurable disease per RECIST Version 1.1 (expansion phase only).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Expected survival of more than 12 weeks.
  • 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:

  • Absolute neutrophil count (ANC) < 1.5×109/L, platelet count < 100 ×109/L, or hemoglobin < 90 g/L.
  • Serum total bilirubin > 1.5 times the upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) aspartate aminotransferase (AST) > 1.5 ULN in patients without hepatic metastases or ALT, AST > 3 ULN in patients with hepatic metastases.
  • Serum potassium, calcium, or magnesium levels out of the normal laboratory reference range, and clinically significant in the investigator's judgment.
  • Serum creatinine clearance < 60 mL/min.
  • 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.
  • Uncontrolled hypertension, defined as: systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90mmHg.
  • 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).
  • 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.
  • History or presence of hemorrhage from any other site (e.g., hemoptysis or hematemesis) within 2 months prior to screening.
  • History of a thromboembolic event (including DVT, pulmonary embolism, stroke and/or transient ischemic attack) within 12 months prior to screening.
  • Patients with squamous non-small-cell lung cancer (NSCLC).
  • 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%.
  • 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.
  • Concomitant medications with a known risk of causing QT prolongation and/or Torsades de Pointes; source list is continuously updated online at www.qtdrugs.org.
  • Systemic anti-neoplastic therapies within 4 weeks prior to the initiation of investigational treatment, including chemotherapy, radical radiotherapy, hormonotherapy, bio-therapy and immunotherapy.
  • Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of study treatment.
  • 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).
  • Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for alopecia).
  • 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.
  • Known clinically significant history of liver disease, including hepatitis or cirrhosis; current alcohol abuse.
  • Evidence of ongoing or active infection requiring intravenous antibiotics.
  • Women who are pregnant or lactating.
  • Central nervous system (CNS) metastatic disease or prior cerebral metastasis.
  • 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.
  • 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 undue risk of harm.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Tanios Bekaii-Saab, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Joleen Hubbard, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Tanios Bekaii-Saab, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20467347

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