Clinical Trials /

A Multi-Center, Open-Label Study of Fruquintinib in Solid Tumors, Colorectal, and Breast Cancer

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, metastatic colorectal cancer and metastatic breast cancer.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Multi-Center, Open-Label Study of Fruquintinib in Solid Tumors, Colorectal, and Breast Cancer
  • Official Title: A Multi-Center, Open-Label, Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anticancer Activity of Fruquintinib in Patients With Advanced Solid Tumors

Clinical Trial IDs

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

Conditions

  • Advanced Solid Tumors
  • Metastatic Colon Cancer
  • Metastatic Breast Cancer
  • Triple Negative Breast Cancer
  • HER2-negative Breast Cancer
  • Hormone Receptor Positive Breast Carcinoma
  • Rectal Cancer

Interventions

DrugSynonymsArms
Fruquintinib (HMPL-013)HMPL-0133 mg Dose Escalation

Purpose

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

Detailed Description

      The study is an open-label, dose escalation and expansion clinical trial to evaluate the
      safety, tolerability, and PK of fruquintinib in patients with advanced solid tumors. The
      study will consist of two phases:

        -  A dose escalation phase - A 3+3 design will be used for this portion of the study.

        -  A dose expansion phase - Five cohorts will be evaluated in Dose Expansion. Cohort A will
           evaluate the MTD/RP2D in patients with advanced solid tumors. Cohort B and Cohort C will
           evaluate the MTD/RP2D in metastatic colorectal cancer patients. Cohort D and Cohort E
           will evaluate the MTD/RP2D in metastatic breast cancer patients.

      Study will be conducted in up to 9 sites in the US.
    

Trial Arms

NameTypeDescriptionInterventions
3 mg Dose EscalationExperimental3 mg of Fruquintinib (HMPL-013), tablet taken daily, 3 weeks on, 1 week off
  • Fruquintinib (HMPL-013)
5 mg Dose EscalationExperimental5 mg of Fruquintinib (HMPL-013), tablet taken daily, 3 weeks on, 1 week off
  • Fruquintinib (HMPL-013)
Fruquintinib Expansion Cohort AExperimental5 mg fruquintinib (HMPL-013) tablet taken daily, 3 weeks on, 1 week off in patients with advanced solid tumors.
  • Fruquintinib (HMPL-013)
Metastatic Colorectal Cancer Expansion Cohort BExperimental5 mg fruquintinib (HMPL-013) tablet taken daily, 3 weeks on, 1 week off in patients with metastatic colorectal cancer who have progressed on or had intolerable toxicity to TAS-102, regoragenib, or both.
  • Fruquintinib (HMPL-013)
Metastatic Colorectal Cancer Expansion Cohort CExperimental5 mg fruquintinib (HMPL-013) tablet taken daily, 3 weeks on, 1 week off in patients with metastatic colorectal cancer who have not been treated with TAS-102 or regorafenib.
  • Fruquintinib (HMPL-013)
Metastatic Breast Cancer Expansion Cohort DExperimental5 mg fruquintinib (HMPL-013) tablet taken daily, 3 weeks on, 1 week off in patients with metastatic Her2-negative, hormone receptor positive breast cancer.
  • Fruquintinib (HMPL-013)
Metastatic Breast Cancer Expansion Cohort EExperimental5 mg fruquintinib (HMPL-013) tablet taken daily, 3 weeks on, 1 week off in patients with metastatic triple negative (Her2-negative, ER-negative, PR-negative) breast cancer.
  • Fruquintinib (HMPL-013)

Eligibility Criteria

        Key Inclusion Criteria:

          -  Fully understand the study and voluntarily sign the ICF;

          -  ≥18years of age;

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

        Dose Escalation Phase:

        • Histologically or cytologically documented, locally advanced or metastatic solid
        malignancy of any type (except squamous NSCLC) that has progressed on approved systemic
        therapy, and for whom no effective therapy or standard of care exists. This cohort is
        closed to enrollment.

        Dose Expansion Phase:

          -  Cohort A: Histologically or cytologically documented, locally advanced or metastatic
             solid malignancy of any type (except squamous NSCLC), that has progressed on approved
             systemic therapy, and for whom no effective therapy or standard of care exists. This
             cohort is closed to enrollment.

          -  Cohort B: Histologically or cytologically documented mCRC in patients that have
             progressed on, or had intolerable toxicity with at least 1 FDA-approved third-line
             systemic therapy (trifluridine/tipiracil or regorafenib). Patients must also have been
             previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based
             chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy for patients
             who had RAS wild-type tumors. This cohort is currently enrolling.

          -  Cohort C: Histologically or cytologically documented adenocarcinoma of the colon or
             rectum. Patients must have progressed on, or had intolerable toxicity to, at least 2
             prior regimens of standard chemotherapy, but must not have received prior TAS-102 or
             regorafenib. Prior therapy could have included adjuvant chemotherapy if a tumor had
             recurred within 6 months after the last administration of treatment. Patients must
             have been previously treated with fluoropyrimidine-, oxaliplatin-, and
             irinotecan-based chemotherapy, an anti-VEGF biological therapy and, if RAS wild-type,
             an anti-EGFR therapy

          -  Cohort D only: Histologically- or cytologically-confirmed Her2-negative, hormone
             receptor positive (ER+ and/or PR+) breast cancer

          -  Cohort E only: Histologically- or cytologically- confirmed triple negative breast
             cancer

        Key Exclusion Criteria:

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

          -  Severe anemia, neutropenia, thrombocytopenia

          -  Moderate to severe renal or hepatic impairment

          -  Uncontrolled hypertension

          -  Risk of, or active hemorrhage: history or presence of active gastric/duodenal ulcer or
             ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history
             of perforation of fistulas; or any other condition that could possibly result in
             gastrointestinal tract hemorrhage or perforation within 6 months prior to screening;

          -  History of a thromboembolic event (including deep vein thrombosis [DVT], pulmonary
             embolism, stroke and/or transient ischemic attack) within 6 months prior to screening;

          -  Patients with squamous 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%;

          -  Patients who have ever received a VEGFR inhibitor, except for patients with mCRC
             enrolled in the dose expansion phase;

          -  Systemic anti-neoplastic therapies 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 (ie, implantation of radioactive seeds) within 60 days prior to the
             first dose of study drug;

          -  Known human immunodeficiency virus (HIV) infection;

          -  Known clinically significant history of liver disease, including cirrhosis, current
             alcohol abuse or active viral hepatitis. For patients with evidence of chronic
             hepatitis B (HBV), the HBV viral load must be undetectable on suppressive therapy, if
             indicated. Patients with a history of hepatitis C virus (HCV) infection must have been
             treated and cured. For patients with HCV who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load;

          -  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
             will be excluded;

          -  No other malignancy, except for non-melanoma skin cancer, 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 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 excipients.

          -  For Cohort C only: patients who have been previously treated with TAS-102 or
             regorafenib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The incidence of DLT in each cohort
Time Frame:At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:The primary endpoint of the dose escalation phase is the incidence of DLT in each cohort.

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:every 4 weeks or every 8 weeks depending on cohort, through study completion, an average of 6 months
Safety Issue:
Description:the proportion of of subjects who have a Complete Response or Partial Response

Details

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

Trial Keywords

  • VEGF
  • colorectal
  • breast

Last Updated

July 6, 2020