Clinical Trials /

CFI-400945 in Patients With Advanced/Metastatic Breast Cancer

NCT03624543

Description:

The standard or usual treatment for this disease is to undergo chemotherapy to slow the spread of the disease and relieve some symptoms of cancer. Patients will have already had at least one chemotherapy treatment for their disease at this stage.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CFI-400945 in Patients With Advanced/Metastatic Breast Cancer
  • Official Title: A Phase II Study of CFI-400945 in Patients With Advanced/Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: I237
  • NCT ID: NCT03624543

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
CFI-400945Cohort 1: TNBC

Purpose

The standard or usual treatment for this disease is to undergo chemotherapy to slow the spread of the disease and relieve some symptoms of cancer. Patients will have already had at least one chemotherapy treatment for their disease at this stage.

Detailed Description

      CFI-400945 is a new type of drug for breast cancer. Laboratory tests show that it works by
      blocking a specific protein called Polo-like Kinase 4 (PLK4) that is involved in cancer cell
      growth. CFI-400945 may slow down the growth of cancer cells or may cause cancer cells to die.
      This drug has been shown to shrink tumours in animals and has been studied in some patients
      and appears well tolerated with little side effects. CFI-400945 seems promising but it is not
      clear if it can offer better results than standard therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: TNBCExperimentalCFI-400945; 64mg, oral, cycle1: day 1-7; 14 day cycle. cycle 2: daily; 28 day cycle N=9 to 24 patients
  • CFI-400945
Cohort 2: PTEN-null, ER+ and/or PR+, HER2-ExperimentalCFI-400945; 64mg, oral, cycle1: day 1-7; 14 day cycle. cycle 2: daily; 28 day cycle N=9 to 24 patients
  • CFI-400945
Cohort 3: Not PTEN-null, ER+ and/or PR+, HER2-ExperimentalCFI-400945; 64mg, oral, cycle1: day 1-7; 14 day cycle. cycle 2: daily; 28 day cycle N=9 to 24 patients
  • CFI-400945

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically and/or cytologically confirmed diagnosis of breast
             cancer, that is advanced/metastatic/recurrent or unresectable, for which no curative
             therapy exists, either:

               -  Negative for ER, PR and HER2 by ASCO/CAP criteria (COHORT 1) OR

               -  Positive for ER and or PR and negative for HER2 AND

                    -  loss or mutation of PTEN, as assessed by IHC assay (COHORT 2) OR

                    -  No loss or mutation of PTEN, as assessed by IHC assay (COHORT 3)

          -  Only female patients will be enrolled.

          -  All patients must have a formalin fixed paraffin embedded tissue block (from primary
             or metastatic tumour) available and must have provided informed consent for the
             release of the block. At least 10 patients per cohort (5 in stage 1 and 5 in stage 2)
             must also have accessible disease suitable for biopsy, have provided informed consent
             for and be willing to undergo a tumour biopsy prior to treatment (after registration),
             again between cycle 2 day 15- day 22.

          -  Presence of clinically and/or radiologically documented disease. All radiology studies
             must be performed within 21 days prior to registration (within 28 days if negative).

          -  All patients must have measurable disease as defined by RECIST 1.1. The criteria for
             defining measurable disease are as follows: Chest x-ray v 20 mm CT scan (with slice
             thickness of 5 mm) ≥ 10 mm --> longest diameter Physical exam (using calipers) ≥ 10 mm
             Lymph nodes by CT scan ≥ 15 mm --> measured in short axis

          -  Patients must be ≥ 18 years of age.

          -  Patients must have an ECOG performance status of 0 or 1.

          -  Patients must have a life expectancy of 3 months or longer.

          -  Laboratory Requirements (must be done within 7 days prior to registration) Absolute
             neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Bilirubin < 1.5 x ULN (upper limit
             of normal) AST and ALT ≤ 2.5 x ULN; ≤ 5.0 x ULN if patient has liver metastases Serum
             creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 60 mL/min

          -  Patients must be able to swallow oral medications and have no known gastrointestinal
             disorders that may interfere with absorption (such as malabsorption).

          -  Patients must have had at least 1 prior line of cytotoxic chemotherapy for breast
             cancer, in any setting, which must have included an anthracycline and a taxane (unless
             contraindicated). There is no limit to the number of prior chemotherapy regimens

          -  Patients may have received other therapies including endocrine therapy, immunotherapy,
             and/or targeted therapies (including CDK4/6 inhibitors).

          -  Patients must have recovered (to at least grade 0 or 1) from all reversible toxicity
             related to prior chemotherapy or systemic therapy and have adequate washout as
             follows:

          -  Longest of one of the following:

               -  Two weeks,

               -  5 half-lives for investigational agents

               -  Standard cycle length of standard therapies.

          -  Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks)
             have elapsed between the last dose of radiation and date of registration. Exceptions
             may be made for low-dose, non-myelosuppressive radiotherapy after consultation with
             CCTG. Concurrent radiotherapy is not permitted.

          -  Patient consent must be appropriately obtained in accordance with applicable local and
             regulatory requirements. Each patient must sign a consent form prior to enrollment in
             the trial to document their willingness to participate.

          -  Patients must be accessible for treatment and follow up. Patients registered on this
             trial must be treated and followed at the participating centre. This implies there
             must be reasonable geographical limits (for example: 1 ½ hour's driving distance)
             placed on patients being considered for this trial.

          -  Women of childbearing potential must have agreed to use a highly effective
             contraceptive method

        Exclusion Criteria:

          -  Patients with a history of other malignancies, except: adequately treated non-melanoma
             skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
             curatively treated with no evidence of disease for > 2 years and which do not require
             ongoing treatment.

          -  Patients with active or uncontrolled infections or with serious illnesses or medical
             conditions which would not permit the patient to be managed according to the protocol.

          -  Patients are not eligible if they have a known hypersensitivity to the study drug(s)
             or their components.

          -  Patients with HER2 positive breast cancer (based on the most recent assessment).

          -  Patients with significant cardiac (including uncontrolled hypertension) or pulmonary
             disease, or active CNS disease or infection. Patients should have a LVEF ≥ 50%.

          -  Patients may not receive concurrent treatment with other anti-cancer therapy (other
             than bone-targeted therapy, if already taking and stable) or investigational agents
             while on protocol therapy.

          -  Patients who have received growth factors within 28 days prior to initiation of dosing
             of CFI-400945 or who will require treatment with growth factors throughout the
             duration of the trial.

          -  Pregnant or breastfeeding women.

          -  Patients being treated with drugs listed in Appendix V Table 1 are excluded. Patients
             being treated with drugs listed in Appendix V Table 2 may be enrolled, but should be
             monitored carefully for toxicities resulting from potential interactions between
             CFI-400945m and these drugs. In addition, patients must avoid consumption of the fruit
             or juice of Seville oranges (e.g. marmalade), grapefruit, pomelos and star fruit from
             7 days before the first dose of study drug and during the entire study due to
             potential CYP3A4 interaction with the study drug. Regular orange juice is allowed.

          -  Patients with history of central nervous system metastases or spinal cord compression
             unless they have received definitive treatment, are clinically stable and do not
             require corticosteroids.

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

          -  Patients being treated with full dose warfarin. Patients with history of deep vein
             thrombosis or pulmonary embolus who are being treated with therapeutic doses of low
             molecular weight heparin, direct factor Xa inhibitors or prophylactic dose
             anticoagulants may be enrolled
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response defined by RECIST 1.1
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Control Rate (DCR) defined by RECIST 1.1
Time Frame:2 years
Safety Issue:
Description:
Measure:Number and severity of adverse events
Time Frame:2 years
Safety Issue:
Description:
Measure:Molecular analyses of CFI-400945 on tumour cells through paired tumour biopsies using next generation DNA sequencing
Time Frame:2 years
Safety Issue:
Description:Molecular analyses including next-generation DNA sequencing will be performed on archival and recent tumour (or normal tissue) materials to identify potential biomarkers of response, histologically assess centrosomes and aberrant mitoses, and evaluate genomic alterations and other molecular features (i.e. gene or protein expression levels).
Measure:Molecular analyses of CTI-400945 on tumour cells through paired biopsies using immunohistochemistry
Time Frame:2 years
Safety Issue:
Description:Assessment of centrosomes and aberrant mitoses and evaluation of genomic alterations and other molecular features (i.e. gene or protein expression levels) by molecular analyses including immunohistochemistry performed on archival and recent tumour (or normal tissue) materials to identify potential biomarkers of response.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Canadian Cancer Trials Group

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