Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-100
SponsorFundacao Champalimaud
About this trial
Phase II, randomized, Active-controlled open label trial for treatment of high risk, HR-/HER2- (triple negative) breast cancer, with two sequences of neoadjuvant chemotherapy on a background of pembrolizumab
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
Be a female or male participant who is at least 18 years of age on the day of signing informed consent.
Have locally histologically confirmed diagnosis of invasive carcinoma of the breast that is classified as TNBC, as defined by the most recent ASCO/CAP guidelines.
Has locally confirmed tumor infiltrating lymphocytes (stromal) (sTILs) equal to or above 10%, as defined by the most recent International Guidelines on TIL Assessment in Breast Cancer.
Disqualifiers
Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
Trial design
Design model
Parallel
Treatments tested in this trial
Pembrolizumab injection
Drug(KXCb - PA\[E\]C) vs (KPA\[E\]C - KXCb) Pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab in the adjuvant setting vs Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab in the adjuvant setting
Treatment groups
20 Participants
are divided into 2 treatment groupsGroup A: Arm 1: (KXCb - PA[E]C)Active comparator 1 intervention
Group B: (KPA[E]C - KXCb)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Detect immunologic activation signal and the immunologically defined most suitable patient population for the synergistic interaction between pembrolizumab and chemotherapy backbone
Compare signals of immunological activation or a more favorable immunological context beetween T cell subpopulations and transcriptional changes of T cell populations infiltrating tumors at baseline and C2D1
Time frame
At the end of cycle 1 (each cycle is 28 days)2
Rate of pCR
Compare the rate of pCR in subjects with locally advanced TNBC with TILs ≥ 10% in arm A and arm B at cycle 4
Time frame
6 months to one year after subject inclusion3
Primary translational endpoint
Quantification of number of T cells per mm2 with different phenotypes using fate bifurcation as defined as the proportion of TILs with the phenotype T-bet(hi) PD1(mid) CD8+.
Time frame
6 months to one year after subject inclusionSecondary outcomes
1
Changes in the immunogenic phenotype
Determine changes in the immunogenic phenotype by longitudinally evaluating RNA-based gene expression signatures (e.g., tumor inflammation signature expression of granzyme A \[GZMA\] and perforin 1 at baseline and at C2D1.
Time frame
6 months to one year after subject inclusion2
Incidence of treatment relatred Adverse events
Describe the safety and tolerability of the combinations of pembrolizumab plus chemotherapy (either EC/AC or paclitaxel + carboplatin) in the Neoadjuvant and Adjuvant setting throught the CTCAE version 5.0 adverse event evaluation
Time frame
6 months to one year after subject inclusionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: