Early Triple-Negative Breast CancerPhase 2DECREASENCT07857486
Reduction of Neoadjuvant Treatment in Early Triple-Negative Breast Cancer
A Phase 2 study testing Pembrolizumab in people with Early Triple-Negative Breast Cancer, run by Institut Paoli-Calmettes.
Trial summary
This multicenter phase II study evaluates a de-escalation strategy of neoadjuvant chemo-immunotherapy in patients with stage II early triple-negative breast cancer and tumor-infiltrating lymphocytes (TILs) ≥ 30%. Patients will receive 12 weeks of neoadjuvant treatment with carboplatin, paclitaxel, and pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early Triple-Negative Breast Cancer
- What is being tested?
- Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Nov 2032
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged 18 years or older.
- Signed informed consent for study participation.
- Histologically and/or cytologically confirmed invasive triple-negative breast adenocarcinoma (ER and PR < 10%, HER2-negative), documented on all tumor samples.
- Stage II disease: T2-T3N0M0 or T1-T2N1M0.
- Tumor-infiltrating lymphocytes (TILs) ≥ 30% on the initial biopsy (TILs will be assessed according to the recommendations of the International TILs Working Group 2014).
- Availability of tumor tissue samples.
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- ECOG Performance Status ≤ 1.
- No contraindication to neoadjuvant chemotherapy or pembrolizumab.
- Adequate bone marrow function, defined as follows (laboratory assessments performed within 21 days prior to enrollment):
- Absolute neutrophil count ≥ 1,500/μL (1.5 × 10⁹/L) Hemoglobin ≥ 10 g/dL Platelet count ≥ 100,000/μL (100 × 10⁹/L)
- Adequate hepatic function, defined as follows (laboratory assessments performed within 21 days prior to enrollment):
- Total serum bilirubin ≤ 1.5 × ULN; for subjects with known Gilbert's syndrome, ≤ 3 × ULN is permitted AST (SGOT) ≤ 2.0 × ULN ALT (SGPT) ≤ 2.0 × ULN Alkaline phosphatase (ALP) ≤ 2.5 × ULN
- Adequate renal function, defined as follows (laboratory assessments performed within 21 days prior to enrollment):
- Serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m²
- Left ventricular ejection fraction (LVEF) ≥ 50%, assessed by echocardiography. A routine LVEF assessment is acceptable if performed within 28 days prior to the start of screening.
- Adequate serum potassium, magnesium, and calcium levels (> ULN).
- Negative serum pregnancy test at screening for subjects of childbearing potential.
- Women of childbearing potential must agree to use a highly effective method of contraception during the screening period, throughout study treatment, and for at least 7 months after the last administration of study treatment. It is strongly recommended that the male partner of a female participant also use a male condom with spermicide throughout this period.
- Affiliation with, or beneficiary of, a health insurance system.
- Ability to communicate and understand French without difficulty.
Who cannot join
- Metastatic disease at diagnosis.
- Relapse of a previous breast cancer.
- Bilateral breast cancer.
- Invasive breast adenocarcinoma with ER and PR > 10% and/or HER2-positive disease.
- Any other malignancy within the previous 3 years, except for cancers considered adequately treated and at low risk of recurrence.
- Pregnant or breastfeeding women, or women likely to become pregnant due to lack of effective contraception.
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- Contraindication to MRI.
- Diagnosis of immunodeficiency.
- Active autoimmune disease (e.g., inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, multiple sclerosis, celiac disease, Wegener's granulomatosis) requiring systemic treatment within the previous 3 years (i.e., disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- Prior treatment with systemic immunosuppressive medications (except physiologic replacement corticosteroids) within 30 days before the planned start of study treatment.
- Receipt of a live (attenuated) vaccine within 30 days before the planned start of study treatment.
- Active infection, including:
- Tuberculosis (TB); Hepatitis B (known positive hepatitis B surface antigen [HBsAg]). Subjects with past or resolved HBV infection (defined by positive anti-HBc antibodies and negative HBsAg) are eligible; Hepatitis C. Subjects positive for anti-HCV antibodies are eligible only if HCV RNA is negative by polymerase chain reaction (PCR); Human immunodeficiency virus (HIV) infection. HIV-positive subjects are eligible if receiving treatment and having an undetectable viral load.
- Significant cardiovascular disease, including New York Heart Association (NYHA) Class II or higher heart disease, cardiomyopathy, acute inflammatory heart disease, myocardial infarction, transient ischemic attack (TIA), stroke within the previous 3 months, unstable arrhythmias, and/or unstable angina.
- Participation in another study involving one or more investigational medicinal products within 3 weeks before study entry (or within a period equivalent to 5 half-lives before the first dose of the study intervention). Participation in observational studies or long-term follow-up of other studies is permitted provided that no procedures likely to interfere with the interpretation of the present study results are performed.
- Prior systemic therapy or curative radiotherapy for the current breast cancer.
- Ongoing acute urinary tract infection, pre-existing hemorrhagic cystitis, or known urinary tract obstruction.
- Known or suspected hypersensitivity, or severe allergy, to any active substance or excipient of the study drugs, including lactose.
- Any uncontrolled medical condition, neuropsychiatric disorder, or significant substance dependence that, in the opinion of the Principal Investigator, could interfere with study completion.
- Vulnerable persons as defined under Article L.1121-6 of the French Public Health Code, adults under legal protection measures, or individuals unable to provide informed consent in accordance with Article L.1121-8 of the French Public Health Code.
- Current use of St. John's Wort (Hypericum perforatum).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Jihane PAKRADOUNI, Director of the Department of contact
About this study
Official title: De-Ecalating Neoadjuvant Chemoimmunotherapy in Early Triple-negative BREASt Cancer
This multicenter phase II study evaluates a de-escalation strategy of neoadjuvant chemo-immunotherapy in patients with stage II early triple-negative breast cancer and tumor-infiltrating lymphocytes (TILs) ≥ 30%. Patients will receive 12 weeks of neoadjuvant treatment with carboplatin, paclitaxel, and pembrolizumab.
The primary objective is to assess the efficacy of this treatment strategy by evaluating the proportion of patients with no suspected residual tumor on breast MRI and biopsy after 12 weeks of neoadjuvant therapy, confirmed by pathological examination of the surgerey sample.
Read the detailed description
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. The KEYNOTE-522 trial established neoadjuvant chemotherapy combined with pembrolizumab as a standard treatment for patients with stage II-III TNBC, resulting in improved pathological complete response rates and survival outcomes. However, this treatment approach is associated with substantial toxicity, which may lead to treatment discontinuation and long-term adverse effects.
Patients who achieve a pathological complete response have an excellent prognosis, supporting the development of treatment de-escalation strategies. High levels of tumor-infiltrating lymphocytes (TILs) are associated with increased response rates and favorable outcomes in TNBC.
This multicenter, prospective, phase II, non-comparative study aims to evaluate a de-escalated neoadjuvant treatment strategy in patients with stage II TNBC and TILs ≥30%. Participants will receive 12 weeks of neoadjuvant treatment with carboplatin, paclitaxel, and pembrolizumab.
The primary objective is to evaluate the proportion of patients with no suspected residual tumor on breast MRI and biopsy after 12 weeks of treatment, confirmed by pathological examination at surgery. Secondary objectives include evaluation of event-free survival, overall survival, residual cancer burden, safety, quality of life, fear of cancer recurrence, and the association between imaging findings, TIL levels, and treatment response. Exploratory analyses will investigate potential circulating and tissue biomarkers associated with treatment efficacy.
- Conditions
- Early Triple-Negative Breast Cancer
- Being tested
- Pembrolizumab
- Keywords
- Triple-Negative Breast Cancer Stage II, Neoadjuvant Therapy, Chemo-Immunotherapy, Treatment De-escalation, Pembrolizumab /Carboplatin /Paclitaxel
- 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.
PembrolizumabDrug
Pembrolizumab administered in combination with carboplatin and paclitaxel as neoadjuvant treatment ( 12 weeks) for stage II early triple-negative breast cancer.
| Study group | Role | What they receive |
|---|---|---|
| De-escalated Neoadjuvant Chemo-Immunotherapy | Experimental | Participants receive neoadjuvant treatment with carboplatin, paclitaxel, and pembrolizumab for 12 weeks as part of a treatment de-escalation strategy for stage II early triple-negative breast cancer with tumor-infiltrating lymphocytes (TILs) ≥30%. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Without Residual Tumor After 12 Weeks of Neoadjuvant Treatment
Proportion of patients with no suspected residual tumor on breast MRI and biopsy after 12 weeks of neoadjuvant treatment, confirmed by pathological examination at surgery.
Measured: 12 weeks
Secondary outcomes (9)
Event-Free Survival (EFS)
Event-free survival.
Measured: 3 years
Overall Survival (OS)
Overall survival.
Measured: 3 years
Residual Cancer Burden (RCB)
Residual Cancer Burden (RCB) will be calculated as a continuous index combining pathological measurements of the primary tumor (size and cellularity) and nodal metastases (number and size), according to the method described by Symmans et al. RCB-0 is defined as pathological complete response (pCR; ypT0/Tis ypN0). RCB-1 corresponds to minimal residual disease, RCB-2 to moderate residual disease, and RCB-3 to extensive residual disease.
Measured: At surgery
Treatment-Related Toxicity
Toxicity related to chemotherapy and immunotherapy will be assessed according to the occurrence and severity of adverse events of interest associated with chemotherapy and pembrolizumab treatment.Incidence of Adverse Events
Measured: Up to 51 weeks
Quality of Life will be assessed
Quality of life will be assessed using the EORTC QLQ-C30 questionnaire at baseline, before surgery, and 3 months after surgery,
Measured: From baseline up to 3 years
Fear of Cancer Recurrence
Fear of cancer recurrence will be assessed using the French version of the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), a 9-item questionnaire, at baseline, before surgery, and at each post-treatment follow-up visit over a 3-year period.
Measured: From baseline up to 3 years
Correlation Between Complete Response on Breast Magnetic Resonance Imaging and Residual Cancer Burden 0 (RCB-0)
Complete response assessed by breast magnetic resonance imaging (MRI) will be compared with pathological complete response assessed by Residual Cancer Burden (RCB) classification. Pathological complete response is defined as RCB-0. The proportion (%) of patients with MRI complete response among patients classified as RCB-0 at surgery will be evaluated..
Measured: At surgery
Association Between Baseline TILs and Residual Cancer Burden
Pre-treatment tumor-infiltrating lymphocyte (TIL) levels, analyzed as both continuous and dichotomous variables, will be compared across RCB-0, RCB-1, and RCB-2/3 categories.
Measured: Baseline and at surgery
Quality of life assessed by EQ-5D-5L
EQ-5D-5L questionnaire at each follow-up visit over a 3-year period.the EQ-5D-5L descriptive system consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five response levels. Responses are converted into a single index value, with scores typically ranging from less than 0 (health states worse than death) to 1.0 (full health). Higher scores indicate better health-related quality of life.
Measured: From baseline up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionFeb 2029 (estimated)
- Study completionNov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early Triple-Negative Breast CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- LORENE SEGUIN, MD, Principal investigator, Paoli-Calmettes Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07857486
- Sponsor's protocol ID
- DECREASE-IPC 2025-068
- Other IDs
- 2025-525040-18-00, 2025
- Acronym
- DECREASE
- Status last verified
- Sep 2026
- First submitted
- 3 Aug 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided