Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Neoplasm, Residual

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patient will have blood samples collected for ctDNA analysis every 3 months for up to 2 years from starting ctDNA screening.

Patients 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.

Nick Turner

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.

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.

atients 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 the patient will be randomised by the 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 to the treatment arm.

For patients allocated to the observation group, the treating team and patient will not be informed that randomisation has taken place in order to remain blinded to the positive ctDNA result. Such patients will continue to have blood samples collected for ctDNA analysis every 3 months up to 2 years from starting ctDNA screening.

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

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

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.

Time from first positive ctDNA detection to disease recurrence or disease-free survival event.

The relationship between sustained clearance of ctDNA on pembrolizumab and biological markers will be summarised and investigated using logistic regression.

Relationship between lead time and clinical/biological factors will be assessed using standard statistical techniques for time to event data.

Relationship between ctDNA clearance and time to recurrence in the pembrolizumab group will be assessed using standard statistical techniques for time to event data.

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

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

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

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

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

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.

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

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

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

Spots Global Cancer Trial Database for intermediate endpoint