Circadian Rhythm Impact on TNBC Response to Neoadjuvant Immunotherapy (CIRCADIAN)

March 15, 2025 updated by: Alexandra Guedes, Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / 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 Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Portugal
    • Região
      • Vila Nova de Gaia, Região, Portugal, 4434-502
        • Recruiting
        • Centro Hospitalar Vila Nova de Gaia/Espinho
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Morning Group
All three neoadjuvant pembrolizumab cycles in the morning (before noon)
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).
No Intervention: Afternoon Group
All three neoadjuvant pembrolizumab cycles in the afternoon (after noon)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response rate
Time Frame: At the time of definitive surgery.
Defined as ypT0/Tis ypN0, assessed by the local pathologist.
At the time of definitive surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2024

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

March 11, 2025

First Submitted That Met QC Criteria

March 11, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 15, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 143/2024

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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