A trial using ctDNA mutation tracking to detect cancer cells in the blood of patients with triple negative breast cancer who have completed standard treatment

Phase 1

• Conditions: Early stage triple negative breast cancer; MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000508-92-GB
• Lead Sponsor: The Institute of Cancer Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-22
• Last Update Posted: 6 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Inclusion criteria for all patients:
1.Signed Informed Consent Form for Registration
2.Male or female patients ages 16 years or older
3.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 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 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:
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 (no neoadjuvant chemotherapy received):
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.
7. 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 receiving adjuvant capecitabine must register before starting capecitabine.
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 allocated 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

Exclusion Criteria

Exclusion criteria for all patients:
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 PDL1, 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 or allogenic stem cell 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.
16. A pathological complete response (pCR) to neoadjuvant chemotherapy

Additional exclusion criteria for pembrolizumab treatment:
1. Diagnosis of an additional cancer since enrolment in the trial other than basal cell carcinoma of the skin or cervical carcinoma in situ
2. Prior chemotherapy, targeted small molecule therapy or radiation therapy within 4 weeks prior to first administration of pembrolizumab, with the exception of planned locoregional adjuvant radiotherapy.
3. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first administration of pembrolizumab.
4. Has not recovered (= Grade 1 or patient’s baseline) from adverse events due to a previously administered therapy. Note: Patients with = grade 2 neuropathy or alopecia of any grade are an exception to this criterion and may qualify for the trial. If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the surgery prior to randomisation.
5. Treatment with an unlicensed or investigational product within 4 weeks prior to first administration of pembrolizumab
6. Received a live vaccine within 30 days of planned start of pembrolizumab. (seasonal flu vaccines are generally inactivated and are permitted; however intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated vaccines and are not permitted.)
7. Presence of any systemic illness incompatible with participation in the clinical trial or inability to provide written informed consent.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified