Clinical Trials /

A Trial Using ctDNA Blood Tests to Detect Cancer Cells After Standard Treatment to Trigger Additional Treatment in Early Stage Triple Negative Breast Cancer Patients

NCT03145961

Description:

c-TRAK TN is a multi-centre phase II study, consisting of a circulating tumour DNA (ctDNA) screening component and a therapeutic component. c-TRAK TN aims to assess whether ctDNA screening can be used to detect residual disease following patients standard primary treatment for triple negative breast cancer, and will assess the safety and activity of the investigational medicinal product pembrolizumab.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial Using ctDNA Blood Tests to Detect Cancer Cells After Standard Treatment to Trigger Additional Treatment in Early Stage Triple Negative Breast Cancer Patients
  • Official Title: c-TRAK TN: A Randomised Trial Utilising ctDNA Mutation Tracking to Detect Minimal Residual Disease and Trigger Intervention in Patients With Moderate and High Risk Early Stage Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: ICR-CTSU/2016/10058
  • SECONDARY ID: 2017-000508-92
  • NCT ID: NCT03145961

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab Treatment

Purpose

c-TRAK TN is a multi-centre phase II study, consisting of a circulating tumour DNA (ctDNA) screening component and a therapeutic component. c-TRAK TN aims to assess whether ctDNA screening can be used to detect residual disease following patients standard primary treatment for triple negative breast cancer, and will assess the safety and activity of the investigational medicinal product pembrolizumab.

Detailed Description

      Patients will undergo blinded serial ctDNA screening every 3 months from the point of
      registration and completion of primary treatment for their triple negative breast cancer. If
      a ctDNA positive result occurs on or before their 12 month ctDNA screening assessment they
      will be randomised by the Institute of Cancer Research Clinical Trials and Statistics Unit
      (ICR-CTSU) in a 2:1 ratio to the pembrolizumab treatment arm or observation arm. The patient
      and their treating team will only be informed of the randomisation if they are allocated
      treatment.

      Patients without a positive ctDNA result within 12 months of starting ctDNA screening, will
      not be randomised but will continue to have blinded ctDNA screening every 3 months up to 2
      years from starting ctDNA screening.

      All patients will be followed up every 6 months until recurrence, specific withdrawal of
      consent for follow up, or until sponsor advises no further follow up is required.
    

Trial Arms

NameTypeDescriptionInterventions
ObservationNo InterventionPatient will have blood samples collected for ctDNA analysis every 3 months for up to 2 years from starting ctDNA screening.
    Pembrolizumab TreatmentExperimentalPatients will be given pembrolizumab every 3 weeks for up to a maximum of 12 months, with blood samples collected prior to each cycle for continued ctDNA analysis. Following treatment discontinuation, blood samples will be collected for ctDNA analysis every 3 months for a further 12 months.
    • Pembrolizumab

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Signed Informed Consent Form for Registration
    
              2. Male or female patients ages 16 years or older
    
              3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
    
              4. Histologically proven primary triple negative breast cancer as defined as oestrogen
                 receptor (ER) negative, progesterone receptor (PgR) negative (if available, otherwise
                 PgR unknown), (as defined by Allred score 0/8 or 2/8 or stain in <1% of cancer cells)
                 and human epidermal growth factor receptor 2 (HER2) negative (immunohistochemistry
                 0/1+ or negative by in situ hybridization) as determined by local laboratory.
    
              5. Availability of tissue from two archival tumour tissue samples (either from diagnostic
                 biopsy, and/or primary surgery. If only one tumour sample is available, the site
                 should inform the ICR-CTSU who will discuss eligibility with the Chief Investigator or
                 the designated Trial Management Group (TMG) member. Patients who have tumours
                 previously sequenced outside the c-TRAK TN trial must provide one archival tumour
                 tissue sample and the report that confirms the mutations detected.
    
              6. Patients with moderate or high risk early stage triple negative breast cancer
                 according to the following risk of relapse criteria:
    
                 High risk criteria:
    
                   1. Neoadjuvant chemotherapy - residual invasive cancer in the axillary node after
                      chemotherapy, defined as at least microscopic residual disease (>0.2mm) by
                      histology, OR One Step Nucleic acid Amplification (OSNA) macroscopic, OR OSNA
                      microscopic with residual invasive cancer in the breast.
    
                   2. Adjuvant chemotherapy - tumour size >50mm and node positive AND/OR ≥4 nodes
                      positive regardless of primary tumour size.
    
                 Moderate risk criteria:
    
                   1. Neoadjuvant chemotherapy - residual invasive cancer in the breast and axillary
                      lymph node negative after chemotherapy
    
                   2. Adjuvant chemotherapy - tumour size >20mm AND/OR involved axillary macroscopic
                      lymph node defined as ≥2mm by histology or OSNA macroscopic.
    
                 Note: Patients who have received both neoadjuvant chemotherapy and further adjuvant
                 chemotherapy must fulfill the adjuvant chemotherapy risk criteria to be eligible on
                 either clinical staging prior to neoadjuvant chemotherapy or pathological staging at
                 surgery.
    
              7. Patients registered according to following criteria for timing of registration
    
                 Neoadjuvant chemotherapy:
    
                 Patients must be registered within 3 months of surgery or within 4 weeks of completing
                 adjuvant radiotherapy if indicated, whichever occurs later. Patients may be registered
                 before or during radiotherapy and should be registered as early as possible.
    
                 Adjuvant chemotherapy:
    
                 Patients must be registered within 3 months of the last cycle of adjuvant
                 chemotherapy, or within 4 weeks of completing adjuvant radiotherapy, whichever occurs
                 later. Patients may register during adjuvant chemotherapy or radiotherapy and should
                 be registered as early as possible.
    
              8. Consent to provide research blood samples.
    
              9. Patients with bilateral tumours can be included if both are triple negative and if two
                 archival tissues samples can be provided per tumour.
    
             10. Patients must have had surgery achieving clear margins (as per local guidelines).
    
             11. Female and male patients of reproductive potential must be willing to use an adequate
                 method of contraception, for the first year of the trial and if randomised to
                 pembrolizumab, for the duration of treatment through to 120 days after the last dose
                 of pembrolizumab. Note: Abstinence is acceptable if this is the usual lifestyle and
                 preferred contraception for the patient.
    
             12. Patients must be willing to have frequent blood tests (every 3 months for 2 years in
                 ctDNA screening and 3 weekly if subsequently allocated pembrolizumab) and receive a 12
                 month course of pembrolizumab if randomised to pembrolizumab treatment on ctDNA
                 detection.
    
             13. No evidence of distant metastatic disease on staging scans conducted at any time since
                 initial diagnosis
    
            NB: Additional eligibility criteria apply to confirm eligibility to commence pembrolizumab
            treatment following randomisation.
    
            Exclusion Criteria:
    
              1. Any concurrent or planned treatment for the current diagnosis of breast cancer other
                 than surgery, locoregional adjuvant radiotherapy, standard neoadjuvant or adjuvant
                 chemotherapy, or a bisphosphonate/denosumab.
    
              2. Prior treatment with a programmed death ligand 1(PDL1), programmed cell death protein
                 1 (PD1), or other immunomodulatory therapy.
    
              3. Prior diagnosis of cancer including prior diagnosis of breast cancer in the previous 5
                 years, other than for basal cell carcinoma of the skin or cervical carcinoma in situ
    
              4. Patients previously entered into a therapeutic trial during or after neoadjuvant
                 chemotherapy where experimental therapy is continued post-surgery.
    
              5. Treatment with an unlicensed or investigational product within 4 weeks of trial entry.
    
              6. Active autoimmune disease requiring systemic therapy in the last two years (i.e. with
                 use of disease modifying agents, corticosteroids or immunosuppressive drugs).
                 Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement
                 therapy for adrenal or pituitary insufficiency) is not considered a form of such
                 systemic treatment.
    
              7. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
                 of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
    
              8. Known history of active Tuberculosis Bacillus (TB).
    
              9. Known history of Human Immunodeficiency Virus (HIV).
    
             10. Known active Hepatitis B or Hepatitis C.
    
             11. Known history of, or any evidence of active, non-infectious pneumonitis.
    
             12. Active infection requiring systemic therapy.
    
             13. Previous solid organ transplantation
    
             14. Females who are pregnant or breastfeeding.
    
             15. Presence of any systemic illness incompatible with participation in the clinical trial
                 or inability to provide written informed consent.
    
            NB. Additional exclusion criteria apply to confirm eligibility to commence pembrolizumab
            treatment following randomisation.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:16 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Positive ctDNA detection by 12 months
    Time Frame:12 months
    Safety Issue:
    Description:The proportion of patients with ctDNA positivity by 12 months as assessed by the blood sample taken at that timepoint

    Secondary Outcome Measures

    Measure:Time to ctDNA detection
    Time Frame:Baseline to first ctDNA positivity (up to a maximum of 12 months after starting ctDNA screening)
    Safety Issue:
    Description:The time from entry into ctDNA screening to first positive ctDNA detection
    Measure:Detection of overt metastatic disease at time of first ctDNA detection in patients allocated to pembrolizumab
    Time Frame:Baseline to first ctDNA positivity (up to a maximum of 12 months after starting ctDNA screening)
    Safety Issue:
    Description:Proportion of patients with metastatic disease at the same time point as first positive ctDNA detection
    Measure:Lead time between ctDNA detection and disease recurrence in the pembrolizumab treatment and observation groups
    Time Frame:From date of randomisation to recurrence detection, expected to occur up to 5 years
    Safety Issue:
    Description:The time between randomisation to the therapeutic aspect of the trial (either to pembrolizumab treatment or observation group) and first confirmed detection of recurrent disease.
    Measure:Absence of detectable ctDNA or disease recurrence after 12 months in the observation group
    Time Frame:12 months after randomisation
    Safety Issue:
    Description:Proportion of patients without detectable ctDNA or disease recurrence 12 months after randomisation to observation group
    Measure:Safety and tolerability of pembrolizumab assessed using NCI CTCAE v4.0, and the proportion of patients reporting dose reductions or delays.
    Time Frame:Throughout pembrolizumab treatment, up to 12 months of treatment
    Safety Issue:
    Description:Adverse events assessed throughout treatment period, using the NCI CTCAE v4.0. Proportion of patients reporting a dose reduction or delay will be presented.
    Measure:Commencement of treatment in patients randomised to receive pembrolizumab
    Time Frame:At point of commencement or non-commencement of treatment, up to 8 weeks following randomisation
    Safety Issue:
    Description:Proportion of patients randomised to receive pembrolizumab who start the therapy.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Institute of Cancer Research, United Kingdom

    Trial Keywords

    • Breast cancer early stage
    • circulating tumour DNA
    • pembrolizumab
    • targeted therapy
    • randomised clinical trial
    • phase II
    • mutation screening
    • intermediate endpoint

    Last Updated

    January 26, 2018