Circadian Rhythm Impact on TNBC Response to Neoadjuvant Immunotherapy
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Morning pembrolizumab infusions.
- Who it may be relevant to
- Registry conditions: Triple Negative Breast Cancer (TNBC). Basic parameters: 18 years — 75 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Portugal
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Circadian Rhythm Impact on Triple Negative Breast Cancer Response to Neoadjuvant Immunotherapy - a Feasibility Randomized Trial
Overview
CIRCADIAN is a prospective randomized clinical trial designed to evaluate the impact of pembrolizumab infusions' time-of-day on pathological complete response (pCR) rate among TNBC patients undergoing neoadjuvant treatment.
Detailed description
Patients will be randomized 1:1 to receive all neoadjuvant pembrolizumab cycles (400 mg every 6 weeks) before versus after noon. Subjects will be stratified based on clinical stage at diagnosis (St. II vs III).
Primary outcome will be pCR rate. As a secondary outcome, we will assess for treatment related toxicity.
For planned exploratory circadian rhythm evaluation, daily body temperature and salivary cortisol variation will be measured before each ICI infusion and the Munich Chronotype Questionnaire (MCTQ) will be applied. To assess for emotional stress, physical exercise habits, stimulating substances use and light exposure, patients will also be subjected to the Distress Thermometer and a lifestyle questionnaire. For planned exploratory biomarker research, tumor infiltrating lymphocytes (TILs) analysis will be performed on the initial diagnostic biopsy and after surgery, on residual tumor (in patients not achieving pCR). Cytokine quantification and bulk RNA sequencing plus flow cytometry studies for immune populations profiling will be performed on peripheral blood, at baseline and before surgery, to check for potential biomarkers of circadian modulation.
Interventions
- Other Morning pembrolizumab infusions
Patients will be randomized 1:1 to receive all three neoadjuvant pembrolizumab cycles in the morning (before noon) or in the afternoon (after noon).
Primary outcome measures
- Pathological complete response rate [Time frame: At the time of definitive surgery.]
Eligibility criteria
Inclusion criteria
- Female sex
- Age 18 - 75 years old
- Diagnosed with Stage II or III TNBC and candidates for neoadjuvant treatment with ChT+pembrolizumab after multidisciplinary group discussion.
Exclusion criteria
- Patients unable to understand or consent to the study;
- Patients not completing ≥2 cycles of planned neoadjuvant pembrolizumab cycles or ≥50% of planned neoadjuvant ChT cycles;
- Patients under daily ≥10 mg of prednisolone or equivalent
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Portugal · 1 center
- Centro Hospitalar Vila Nova de Gaia/Espinho — Vila Nova de Gaia
Identifiers
NCT: NCT06880029 · 143/2024