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 | Unknown Phase 2 DMC

• 2 other identifiers: ICR-CTSU/2016/100582017-000508-92
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 17

Brief 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 will assess the safety and activity of the investigational medicinal product pembrolizumab.

Conditions

Triple Negative Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

  12 months

• 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

  24 months

• 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

  6 months (24 weeks) after commencing pembrolizumab

Secondary Outcomes (6)

• Time to ctDNA detection

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

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

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

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

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

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

  6 months after randomisation

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

  Throughout pembrolizumab treatment, up to 12 months of treatment

Other Outcomes (4)

• Descriptive differences in time between ctDNA detection and disease recurrence, and disease free survival, between patients in the pembrolizumab and the observation groups

  Time between first ctDNA detection and documented recurrence or disease free survival event, whichever comes first, expected to occur up to 5 years

• To explore predictors of sustained ctDNA clearance on pembrolizumab.

  6-12 months after commencing pembrolizumab

• To explore potential predictors of relapse and ctDNA detection, and alternative definitions of ctDNA clearance

  Baseline to point of disease recurrence, expected to occur up to 5 years

Study Arms (2)

Observation

NO INTERVENTION

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

Pembrolizumab Treatment

EXPERIMENTAL

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.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200mg intravenous infusion

Also known as: Keytruda

Pembrolizumab Treatment

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• National Institute for Health Research Biomedical Research Centre at the Royal Marsden / Institute of Cancer Research UK: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (17)

Royal Marsden Hospital, Chelsea

Chelsea, London, SW3 6JJ, United Kingdom

Location

Royal Marsden Hospital, Sutton

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Charing Cross Hospital

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

University College London Hopitals

London, United Kingdom

Location

Maidstone Hospital

Maidstone, ME16 9QQ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Royal Cornwall Hospital

Truro, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36423745 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Nick Turner

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 9, 2017
• Study Start: December 21, 2017
• Primary Completion: September 30, 2021
• Study Completion: March 31, 2024
• Last Updated: February 24, 2022

Record last verified: 2022-02

Locations

GB (17)