Triple Negative Breast Cancer (TNBC)Phase 1/2CIRCADIANNCT06880029
Circadian Rhythm Impact on TNBC Response to Neoadjuvant Immunotherapy
A Phase 1/2 study testing Morning pembrolizumab infusions in people with Triple Negative Breast Cancer (TNBC), run by Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. at 1 site in Portugal.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Triple Negative Breast Cancer (TNBC)
- What is being tested?
- Morning pembrolizumab infusions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 sitePortugal
- Study dates
- 1 Sep 2024to 1 Sep 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal1 site, 1 recruiting
- Recruiting
Centro Hospitalar Vila Nova de Gaia/Espinho
Vila Nova de Gaia, Região, 4434-502
Alexandra P. Guedes, Medical Oncologist M.D., 00351968957977, alexandra95dg@gmail.com
About this study
Official title: Circadian Rhythm Impact on Triple Negative Breast Cancer Response to Neoadjuvant Immunotherapy - a Feasibility Randomized Trial
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.
Read the 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.
- Conditions
- Triple Negative Breast Cancer (TNBC)
- Being tested
- Morning pembrolizumab infusions
- Keywords
- TNBC, Immunotherapy, Circadian rhythm
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Morning pembrolizumab infusionsOther
Patients will be randomized 1:1 to receive all three neoadjuvant pembrolizumab cycles in the morning (before noon) or in the afternoon (after noon).
| Study group | Role | What they receive |
|---|---|---|
| Morning Group | Experimental | All three neoadjuvant pembrolizumab cycles in the morning (before noon) Receives: Other: Morning pembrolizumab infusions |
| Afternoon Group | No intervention | All three neoadjuvant pembrolizumab cycles in the afternoon (after noon) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response rate
Defined as ypT0/Tis ypN0, assessed by the local pathologist.
Measured: At the time of definitive surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2025
- Study start1 Sep 2024
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast Cancer (TNBC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Alexandra Guedes, Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06880029
- Sponsor's protocol ID
- 143/2024
- Acronym
- CIRCADIAN
- Status last verified
- Mar 2025
- First submitted
- 11 Mar 2025
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circadian Rhythm Impact on Triple Negative Breast Cancer Response to Neoadjuvant Immunotherapy - a Feasibility Randomized Trial
- ClinicalTrials.gov ID
- NCT06880029
- Acronym / sponsor ID
- CIRCADIAN / 143/2024
- Conditions
- Triple Negative Breast Cancer (TNBC)
- Keywords
- TNBC, Immunotherapy, Circadian rhythm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.Other government
- Study start
- 1 Sep 2024 (actual)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Sep 2025 (estimated)
- First posted
- 17 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morning Group | Experimental | Other: Morning pembrolizumab infusionsAll three neoadjuvant pembrolizumab cycles in the morning (before noon) |
| Afternoon Group | No intervention | –All three neoadjuvant pembrolizumab cycles in the afternoon (after noon) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Morning pembrolizumab infusionsPatients will be randomized 1:1 to receive all three neoadjuvant pembrolizumab cycles in the morning (before noon) or in the afternoon (after noon). | Other | Morning Group |
Primary outcome
Pathological complete response rate
Time frame: At the time of definitive surgery.
Defined as ypT0/Tis ypN0, assessed by the local pathologist.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
Related trials for Triple Negative Breast Cancer (TNBC)
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingPhase 1/2
A Study of MR001 in Patients With Locally Recurrent or Metastatic Advanced Triple-Negative Breast Cancer (TNBC)
Triple-Negative Breast Cancer (TNBC)
RecruitingPhase 3
Sacituzumab Tirumotecan (MK-2870) Plus Pembrolizumab Versus TPC in TNBC Who Did Not Achieve pCR (MK-2870-012)
Triple-Negative Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Morning pembrolizumab infusions in people with Triple Negative Breast Cancer (TNBC), run by Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexandra P. Guedes, Medical Oncologist M.D. (+351968957977, alexandra95dg@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response rate (time frame: At the time of definitive surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2025.