Clinical Trials /

A Study of CFI-400945 Fumarate in Patients With Advanced Cancer

NCT01954316

Description:

This is a phase 1 study to test different doses of a new investigational drug called CFI-400945 to see which dose is safer in people. This study will also look at the safety of CFI-400945 and to study its effects on patients with advanced cancers. This drug has been tested in animals but not yet in people. CFI-400945 is an oral (taken by mouth) drug that works by blocking polo-like kinase 4 (PLK4) from working. PLK4 is a protein that is important in regulating cell growth and division and cell death. Many tumors are shown to make too much PLK4. When there is too much PLK4 produced, it is believed to lead to uncontrolled cancer cell growth and division. Therefore, by blocking this protein from working, it is believed to stop tumors growing or shrink them.

Related Conditions:
  • Cancer
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CFI-400945 Fumarate in Patients With Advanced Cancer
  • Official Title: An Open Label, Dose Escalation, Safety, and Pharmacokinetic Study of CFI-400945 Fumarate Administered Orally to Patients With Advanced Cancer

Clinical Trial IDs

  • ORG STUDY ID: CFI-400945-CL-001
  • NCT ID: NCT01954316

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
CFI-400945CFI-400945 fumarate

Purpose

This is a phase 1 study to test different doses of a new investigational drug called CFI-400945 to see which dose is safer in people. This study will also look at the safety of CFI-400945 and to study its effects on patients with advanced cancers. This drug has been tested in animals but not yet in people. CFI-400945 is an oral (taken by mouth) drug that works by blocking polo-like kinase 4 (PLK4) from working. PLK4 is a protein that is important in regulating cell growth and division and cell death. Many tumors are shown to make too much PLK4. When there is too much PLK4 produced, it is believed to lead to uncontrolled cancer cell growth and division. Therefore, by blocking this protein from working, it is believed to stop tumors growing or shrink them.

Detailed Description

      All participants will receive CFI-400945. At the beginning of the study, participants are
      given a low dose of CFI-400945 and are watched very closely to see what side effects they
      have and to make sure the side effects are not severe. If the side effects are not severe,
      then more participants are asked to join the study and are given a higher dose of study
      drug. Participants joining the study later on will get higher doses of study drug than
      participants who join earlier. This will continue until the highest dose of study drug that
      can be taken without severe side effects is found (called maximum tolerated dose). Doses
      higher than that will not be given.

      After the best dose of study drug is found, additional participants will be asked to join
      the study and will be given the study drug at the maximum tolerated dose to further test the
      safety and the drug at that dose.
    

Trial Arms

NameTypeDescriptionInterventions
CFI-400945 fumarateExperimentalCFI-400945 fumarate tablets, dose levels 3, 6, 11, 16, 24, and 32 mg/day
  • CFI-400945

Eligibility Criteria

        Inclusion Criteria:

          -  Have histologic or cytological proof of advanced cancer that has progressed and for
             which there is no further standard anticancer therapy available in the opinion of the
             investigator.

          -  Patients must have measurable disease.

          -  Are 18 years of age or older.

          -  Have clinically acceptable laboratory screening results within certain limits

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

          -  Able to swallow oral medications.

          -  Have a life expectancy greater than 3 months.

          -  Women and men of child producing potential must agree to use highly effective means
             of contraception during study participation, and for at least 30 days after the last
             administration of study medication.

          -  Negative serum pregnancy test with 72 hours prior to start of study drug

          -  Have the ability to understand the requirements of the study, provide written
             informed consent which includes authorization for release of protected health
             information, abide by the study restrictions, and agree to return for the required
             assessments.

        Exclusion Criteria:

          -  Women who are pregnant or nursing.

          -  Have received radiotherapy, chemotherapy, biological therapy or investigational
             treatment less than four weeks (six weeks for nitrosourea or mitomycin C) prior to
             first dose of study medication or have not recovered from all acute toxicities from
             prior treatments.

          -  Patients who have received growth factors within 14 days prior to initiation of
             dosing of CFI-400945 fumarate.

          -  Have active, acute, or chronic clinically significant infections.

          -  Have uncontrolled severe hypertension

          -  Have clinical symptomatic congestive heart failure defined at >= Class II of the New
             York Heart Association functional classification system or LVEF < 50% at baseline.

          -  Have active angina pectoris or recent myocardial infarction (within 6 months).

          -  Have chronic atrial fibrillation or QTc of greater than 470 msec, as calculated by
             Bazett's correction formula.

          -  Have had major surgery within 21 days of starting therapy. Placement of a venous
             access device within 21 days of starting therapy is allowed.

          -  Have additional uncontrolled serious medical or psychiatric illness.

          -  Have any medical condition that could impair the administration of oral agents
             including significant bowel resection, inflammatory bowel disease or uncontrolled
             nausea or vomiting.

          -  Known central nervous system metastasis. Patients with history of central nervous
             system metastases are eligible if they are clinically or radiographically stable for
             at least 3 months and not taking steroids or anticonvulsants.

          -  Patients being treated with full dose warfarin are excluded. Patients with history of
             deep vein thrombosis or pulmonary embolus who are being treated with therapeutic
             doses of low molecular weight heparin or prophylactic dose anticoagulants may be
             enrolled.

          -  Patients being treated with certain drugs not acceptable while receiving CFI-400945
             fumarate.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Highest dose level that does not lead to unacceptable toxicity in two or more patients in a dosing group
Time Frame:From first dose of study drug until the date of unacceptable toxicity, up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic profile of CFI-400945 fumarate (please see description below)
Time Frame:Day 1 and Day 28 of Cycle 1 prior to first dose and at 0.5, 1, 2 (± 5 minutes), 4, 6, 8, 10-12 (± 15 minutes), and 24 hours (± 60 minutes) following dosing. Day 1 of Cycle 2 and future cycles, prior to dosing.
Safety Issue:
Description:Area under the plasma concentration-time curve (AUC) Elimination half-life (T½) Maximum plasma concentration (Cmax) Minimum plasma concentration (Cmin) Time when Cmax occurs (Tmax) Average plasma concentration at steady state (Cavg)
Measure:Number of patients with a response to treatment
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of side effects occurring and severity
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Health Network, Toronto

Trial Keywords

  • advanced cancer
  • CFI-400945 fumarate
  • polo-like kinase 4
  • PLK4
  • tablet
  • dose escalation
  • genetic testing

Last Updated

June 21, 2016