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Triple Negative Breast CancerPhase 2c-TRAK-TNNCT03145961

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

A Phase 2 study testing Pembrolizumab in people with Triple Negative Breast Cancer, run by Institute of Cancer Research, United Kingdom at 17 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

c-TRAK TN is a multi-centre phase II study, consisting of a circulating tumour DNA (ctDNA) surveillance component and a therapeutic component. c-TRAK TN aims to assess whether ctDNA surveillance can be used to detect residual disease following patients standard primary treatment for triple negative breast cancer, and… Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
208 participants
Where
17 sitesUnited Kingdom
Study dates
21 Dec 2017to 31 Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Signed Informed Consent Form for Registration.
  • Male or female patients ages 16 years or older.
  • ECOG performance status 0, 1 or 2.
  • 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 HER2 negative (immunohistochemistry 0/1+ or negative by in situ hybridization) as determined by local laboratory.
  • 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 designated 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.
  • Patients with moderate or high risk early stage triple negative breast cancer according to the following risk of relapse criteria:
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  • Neoadjuvant chemotherapy (no adjuvant chemotherapy planned) High risk criteria - Residual microscopic or macroscopic invasive cancer in the axillary nodes after chemotherapy Moderate risk criteria - Residual invasive cancer in the breast, and axillary lymph node negative after chemotherapy Adjuvant chemotherapy High risk criteria - Tumour size >50mm and node positive OR ≥4 nodes positive regardless of primary tumour size.
  • Moderate risk criteria - Tumour size >20mm AND/OR involved axillary macroscopic lymph node.
  • Both neoadjuvant and adjuvant chemotherapy Patients who have received both neoadjuvant chemotherapy and further adjuvant chemotherapy must fulfil only the adjuvant chemotherapy risk criteria to be eligible. They can fulfil the criteria on either clinical staging prior to neoadjuvant chemotherapy or pathological staging at surgery.
  • Patients must be registered according to the following criteria for timing of registration:
  • Neoadjuvant chemotherapy (no adjuvant chemotherapy planned):
  • Patients must be registered within 6 weeks of surgery. Patients may be registered before or during radiotherapy and should be registered as early as possible.
  • Adjuvant chemotherapy (no neoadjuvant chemotherapy received):
  • Patients must be registered before, or on the day of, the 3rd cycle of adjuvant chemotherapy and should be registered as early as possible.
  • Both neoadjuvant and adjuvant chemotherapy Patients must be registered within 6 weeks of surgery. Patients may be registered before or during radiotherapy. Patients must register before starting capecitabine.
  • Consent to provide research blood samples.
  • Patients with bilateral tumours can be included if both are triple negative and if two archival tissues samples can be provided per tumour.
  • Patients must have had surgery achieving clear margins (as per local guidelines).
  • 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 allocated to pembrolizumab, for the duration of treatment through to 120 days after the last dose of pembrolizumab (see appendix 2). Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
  • Patients must be willing to have frequent blood tests (every 3 months for 2 years in ctDNA surveillance and 3 weekly if subsequently allocated pembrolizumab) and receive a 12 month course of pembrolizumab on ctDNA detection.
  • No evidence of distant metastatic disease or local recurrence on staging scans conducted at any time since initial diagnosis.
  • NB: Additional eligibility criteria apply to confirm eligibility to commence pembrolizumab treatment following randomisation.

Who cannot join

  • Any concurrent or planned treatment for the current diagnosis of breast cancer other than surgery, loco regional adjuvant radiotherapy, standard neoadjuvant or adjuvant chemotherapy, or a bisphosphonate/denosumab.
  • Prior treatment with a PDL1, PD1, or other immunomodulatory therapy.
  • 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.
  • Patients previously entered into a therapeutic trial during or after neoadjuvant chemotherapy where experimental therapy is continued post-surgery (see protocol section 15).
  • Treatment with an unlicensed or investigational product within 4 weeks of trial entry.
  • 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.
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  • 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.
  • Known history of active Tuberculosis Bacillus (TB).
  • Known history of Human Immunodeficiency Virus (HIV).
  • Known active Hepatitis B or Hepatitis C.
  • Known history of, or any evidence of active, non-infectious pneumonitis.
  • Active infection requiring systemic therapy.
  • Previous solid organ or allogenic stem cell transplantation.
  • Females who are pregnant or breastfeeding.
  • Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent.
  • A pathological complete response (pCR) to neoadjuvant chemotherapy
  • NB. Additional exclusion criteria apply to confirm eligibility to commence pembrolizumab treatment following randomisation.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United Kingdom17 sites

  • Royal Bournemouth Hospital

    Bournemouth

  • Velindre Cancer Centre

    Cardiff

  • Royal Marsden Hospital, Chelsea

    Chelsea, London, SW3 6JJ

  • Western General Hospital

    Edinburgh

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Guy's Hospital

    London, SE1 9RT

  • Charing Cross Hospital

    London

  • St Bartholomew's Hospital

    London

  • University College London Hopitals

    London

  • Maidstone Hospital

    Maidstone, ME16 9QQ

  • The Christie NHS Foundation Trust

    Manchester

  • Clatterbridge Cancer Centre

    Metropolitan Borough of Wirral

  • Nottingham University Hospitals NHS Trust

    Nottingham

  • Churchill Hospital

    Oxford

  • Weston Park Hospital

    Sheffield

  • Royal Marsden Hospital, Sutton

    Sutton, Surrey, SM2 5PT

  • Royal Cornwall Hospital

    Truro

Other trials in United Kingdom

About this study

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

c-TRAK TN is a multi-centre phase II study, consisting of a circulating tumour DNA (ctDNA) surveillance component and a therapeutic component. c-TRAK TN aims to assess whether ctDNA surveillance 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.

Read the detailed description

During the randomised component of the trial (prior to implementation of protocol v6.0 on 16 Sept 2020), patients would undergo serial ctDNA surveillance every 3 months from the point of registration and completion of primary treatment for their triple negative breast cancer. ctDNA surveillance was blinded and the detection of a ctDNA positive result on or before the 12 month ctDNA surveillance assessment triggered randomisation to treatment with pembrolizumab or observation (on a 2:1 ratio). The patient and their treating team were only informed of the randomisation if allocated treatment.

Patients without a positive ctDNA result within 12 months of starting ctDNA surveillance, continued to have blinded ctDNA surveillance every 3 months up to 2 years total.

Following the implementation of protocol v6.0 (16 Sept 2020), patients were asked to transfer to the non-randomised component of the trial, all patients who were previously randomised to observation and remain in active ctDNA surveillance would transition to the non-randomised component of the trial following re-consent, and allocated pembrolizumab at the next positive ctDNA result.

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

Being tested
Pembrolizumab
Keywords
Breast cancer early stage, circulating tumour DNA, pembrolizumab, targeted therapy, randomised clinical trial, phase II, mutation screening, intermediate endpoint
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03145961
Study groupRoleWhat they receive
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.
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Positive ctDNA detection by 12 months

    The proportion of patients with ctDNA positivity by 12 months as assessed by the blood sample taken at that timepoint

    Measured: 12 months

  2. Positive ctDNA detection by 24 months

    The proportion of patients with ctDNA positivity by 24 months as assessed by the blood sample taken at that timepoint

    Measured: 24 months

  3. Absence of detectable ctDNA or disease recurrence 6 months (24 weeks) after commencing pembrolizumab

    The proportion of patients without either detectable ctDNA or disease recurrence 6 months (24 weeks) after starting pembrolizumab

    Measured: 6 months (24 weeks) after commencing pembrolizumab

Secondary outcomes (6)

  1. Time to ctDNA detection

    The time from entry into ctDNA surveillance to first positive ctDNA detection

    Measured: Baseline to first ctDNA positivity (up to a maximum of 12 months after starting ctDNA surveillance)

  2. Detection of overt metastatic disease at time of first ctDNA detection in patients allocated to pembrolizumab

    Proportion of patients with metastatic disease at the same time point as first positive ctDNA detection

    Measured: Baseline to first ctDNA positivity (up to a maximum of 12 months after starting ctDNA surveillance)

  3. Lead time between ctDNA detection and disease recurrence in the pembrolizumab treatment and observation groups

    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.

    Measured: From date of randomisation to recurrence detection, expected to occur up to 5 years

  4. Absence of detectable ctDNA or disease recurrence after 6 months in the observation group

    Proportion of patients without detectable ctDNA or disease recurrence 6 months after randomisation to observation group

    Measured: 6 months after randomisation

  5. Safety and tolerability of pembrolizumab assessed using NCI CTCAE v4.0, and the proportion of patients reporting dose reductions or delays.

    Adverse events assessed throughout treatment period, using the NCI CTCAE v4.0. Proportion of patients reporting a dose reduction or delay will be presented.

    Measured: Throughout pembrolizumab treatment, up to 12 months of treatment

  6. Commencement of treatment in patients randomised to receive pembrolizumab

    Proportion of patients randomised to receive pembrolizumab who start the therapy.

    Measured: At point of commencement or non-commencement of treatment, up to 8 weeks following randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 May 2017
  2. Study start21 Dec 2017
  3. Primary completion30 Sep 2021
  4. Study completion31 Mar 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
208 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03145961
Sponsor's protocol ID
ICR-CTSU/2016/10058
Other IDs
2017-000508-92, 2017
Acronym
c-TRAK-TN
Status last verified
Feb 2022
First submitted
28 Apr 2017
Last updated
24 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Formal requests for data sharing will be considered in line with ICR-CTSU procedure with due regard given to funder and sponsor guidelines. Requests are via a standard pro forma describing the nature of the proposed research and extent of data requirements. Data recipients are required to sign a data release form which describes the conditions for release and requirements for data transfer, storage, archiving, publication and Intellectual Property.

Publications

  • Turner NC, Swift C, Jenkins B, Kilburn L, Coakley M, Beaney M, Fox L, Goddard K, Garcia-Murillas I, Proszek P, Hall P, Harper-Wynne C, Hickish T, Kernaghan S, Macpherson IR, Okines AFC, Palmieri C, Perry S, Randle K, Snowdon C, Stobart H, Wardley AM, Wheatley D, Waters S, Winter MC, Hubank M, Allen SD, Bliss JM; c-TRAK TN investigators. Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer. Ann Oncol. 2023 Feb;34(2):200-211. doi: 10.1016/j.annonc.2022.11.005. Epub 2022 Nov 22.

    PubMed 36423745

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Triple Negative Breast Cancer, run by Institute of Cancer Research, United Kingdom at 17 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positive ctDNA detection by 12 months (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03145961, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2022.

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