Clinical Trials /

A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Patients With Metastatic Colorectal Cancer

NCT04322539

Description:

This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). Approximately 520 subjects will be randomized to one of the following treatment arms in a 2:1 ratio, fruquintinib plus BSC or placebo plus BSC.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Patients With Metastatic Colorectal Cancer
  • Official Title: A Global Multicenter Randomized Placebo-Controlled Phase 3 Trial To Compare The Efficacy And Safety Of Fruquintinib Plus Best Supportive Care To Placebo Plus Best Supportive Care In Patients With Refractory Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2019-013-GLOB1
  • NCT ID: NCT04322539

Conditions

  • Metastatic Colorectal Cancer
  • Metastatic Colon Cancer

Interventions

DrugSynonymsArms
FruquintinibHMPL-013fruquintinib plus best supportive care
Placeboplacebo plus best supportive care

Purpose

This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). Approximately 520 subjects will be randomized to one of the following treatment arms in a 2:1 ratio, fruquintinib plus BSC or placebo plus BSC.

Detailed Description

      This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical
      trial to compare the efficacy and safety of fruquintinib in combination with BSC versus
      placebo in combination with BSC in advanced colorectal cancer patients who have progressed
      on, or were intolerant to, chemotherapy, biologics, and TAS-102 or regorafenib. Patients with
      MSI-H/MMR deficient tumors must have also received an immune checkpoint inhibitor if approved
      and available and if deemed appropriate.

      Metastatic colorectal cancer cannot be cured by surgery. Therefore, treatment principals are
      primarily aimed at controlling disease progression and prolonging survival. Standard first-
      and second-line therapy includes cytotoxic drugs such as 5-fluorouracil, oxaliplatin, and
      irinotecan; anti-VEGF therapy; and, if RAS wild type, anti-EGFR therapy. After the first two
      lines of chemotherapy, standard third-line treatment is either TAS-102 or regorafenib. There
      are currently no effective treatments for patients who have progressed on standard, approved
      therapies, and treatment options include reuse of prior therapies, clinical trials or BSC.
      Consequently, there is an unmet medical need for additional safe and effective treatment.
    

Trial Arms

NameTypeDescriptionInterventions
fruquintinib plus best supportive careExperimentalIn this arm, subjects will receive active study drug plus best supportive care
  • Fruquintinib
placebo plus best supportive carePlacebo ComparatorIn this arm, subjects will receive placebo plus best supportive care
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Provide written informed consent;

          -  Age ≥18 years;

          -  Histologically and/or cytologically documented metastatic colorectal adenocarcinoma.
             RAS, BRAF, and microsatellite instability microsatellite instability (MSI)/mismatch
             repair (MMR) status for each patient must be documented;

          -  Subjects must have progressed on or been intolerant to treatment with either
             trifluridine/tipiracil (TAS-102) or regorafenib. Subjects are considered intolerant to
             TAS-102 or regorafenib if they have received at least 1 dose of either agents and were
             discontinued from therapy for reasons other than disease progression. Subjects who
             have been treated with both TAS-102 and regorafenib are permitted. Subjects must also
             have been previously treated with standard approved therapies: fluoropyrimidine-,
             oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and,
             if RAS wild-type, an anti-EGFR therapy;

          -  Subjects with microsatellite-high (MSI-H) or mismatch repair deficient (dMMR) tumors
             must have been treated with immune checkpoint inhibitors if approved and available in
             the subject's country unless the patient is ineligible for treatment with a checkpoint
             inhibitor;

          -  Subjects who received oxaliplatin in the adjuvant setting must have progressed within
             6 months of completion of adjuvant therapy;

          -  Body weight ≥40kg;

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

          -  Have measurable disease according to RECIST Version 1.1, assessed locally. Tumors that
             were treated with radiotherapy are not measurable per RECIST Version 1.1, unless there
             has been documented progression of those lesions;

          -  Expected survival >12 weeks.

          -  For female subjects of childbearing potential and male subjects with partners of
             childbearing potential, agreement to use a highly effective form(s) of contraception,
             that results in a low failure rate (<1% per year) when used consistently and
             correctly, starting during the screening period, continuing throughout the entire
             study period, and for 90 days after taking the last dose of study drug. Such methods
             include: oral hormonal contraception (combined estrogen/ progestogen, or
             progestogen-only) associated with inhibition of ovulation together with a barrier
             method (eg, diaphragm, always containing a spermicide), intrauterine device (IUD),
             intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized
             partner, or sexual abstinence. Oral contraception should always be combined with an
             additional contraceptive method (ie, barrier method) because of a potential
             interaction with the study drug. The same criteria are applicable to male subjects
             involved in this clinical trial if they have a partner of childbirth potential, and
             male subjects must always use a condom.

        Exclusion Criteria:

          -  Absolute neutrophil count (ANC) <1.5×109/L, platelet count <100×109/L, or hemoglobin
             <9.0 g/dL. Blood transfusion within 1 week prior to enrollment for the purpose of
             increasing the likelihood of eligibility is not allowed;

          -  Serum total bilirubin >1.5 × the upper limit of normal (ULN). Patients with Gilbert
             syndrome, bilirubin <2 X ULN, and normal AST/ALT are eligible;

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × ULN in
             patients without hepatic metastases; ALT or AST >5 × ULN in patients with hepatic
             metastases;

          -  Serum creatinine >1.5 × ULN or creatinine clearance <60 mL/min. Creatinine clearance
             can either be measured in a 24-hour urine collection or estimated by the
             Cockroft-Gault equation.

          -  Urine dipstick protein ≥2+ or 24-hour urine protein ≥1.0 g/24-h. Subjects with greater
             than 1+ proteinuria on urinalysis must undergo a 24-hour urine collection;

          -  Uncontrolled hypertension, defined as: systolic blood pressure ≥140 mm Hg and/or
             diastolic blood pressure ≥90 mm Hg despite optimal medical management;

          -  International Normalized Ratio (INR) >1.5 x ULN or activated partial thromboplastin
             time (aPTT) >1.5 × ULN, unless the patient is currently receiving or intended to
             receive anticoagulants for prophylactic purposes;

          -  History of, or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage
             of an unresected gastrointestinal tumor, history of perforation or fistulas; or any
             other condition that could, in the investigator's judgment, result in gastrointestinal
             hemorrhage or perforation; within the 6 months prior to screening;

          -  History or presence of hemorrhage from any other site (eg, hemoptysis or hematemesis)
             within 2 months prior to screening;

          -  History of a thromboembolic event, including deep vein thrombosis (DVT), pulmonary
             embolism (PE), or arterial embolism within 6 months prior to screening.

          -  Stroke and/or transient ischemic attack within 12 months prior to screening;

          -  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% by echocardiogram;

          -  Mean corrected QT interval using the Fridericia 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 first-degree relative.

          -  Concomitant medications with a known risk of causing QT prolongation and/or Torsades
             de Pointes.

          -  Systemic anti-neoplastic therapies (except for those described in Exclusion 18) or any
             investigational therapy within 4 weeks prior to the first dose of study drug,
             including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and
             immunotherapy;

          -  Systemic small molecule targeted therapies (eg, tyrosine kinase inhibitors) within 5
             half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;

          -  Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the
             initiation of study drug;

          -  Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the
             first dose of study drug.

          -  Use of strong inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of
             study drug;

          -  Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central
             venous catheter placement is allowed) within 60 days prior to the first dose of study
             drug or unhealed surgical incision;

          -  Any unresolved toxicities from a previous antitumor treatment greater than CTCAE v5.0
             Grade 1 (except for alopecia or neurotoxicity grade≤2).

          -  Known human immunodeficiency virus (HIV) infection;

          -  Known history of active viral hepatitis. For patients with evidence of chronic
             hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on
             suppressive therapy, if indicated. Patients with HCV infection who are currently on
             treatment are eligible if they have an undetectable HCV viral load.

          -  Clinically uncontrolled active infection requiring IV antibiotics;

          -  Tumor invasion of a large vascular structure, eg, pulmonary artery, superior or
             inferior vena cava;

          -  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; patients requiring steroids within 4 weeks prior to start of study treatment
             are excluded;

          -  Other malignancy, except for non-melanoma skin cancer, in situ cervical ca or bladder
             ca (Tis and T1) that have been adequately treated during the 5 years prior to
             screening;

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

          -  Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory
             result, or any other condition (e.g., current alcohol or drug abuse) that
             investigators suspect may prohibit use of the investigational product, affect
             interpretation of study results, or put the patient at undue risk of harm based on the
             investigator's assessment;

          -  Known hypersensitivity to fruquintinib or any of its inactive ingredients.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:up to 10 years
Safety Issue:
Description:To evaluate the overall survival of fruquintinib plus BSC compared to placebo plus BSC in subjects with refractory mCRC.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hutchison Medipharma Limited

Trial Keywords

  • colon
  • colorectal
  • mcrc
  • crc
  • metastatic colon
  • metastatic colorectal
  • VEGF
  • VEGFR

Last Updated

June 4, 2020