2025-525040-18-00RecruitingPhase 2
DECREASE-IPC 2025-068 : De-Ecalating neoadjuvant Chemoimmunotherapy in early triple-negative BREASt cancer
Institut Paoli Calmettes7 sites in 1 country84 target enrollmentStarted: June 15, 2026Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 84
- Locations
- 7
- Primary Endpoint
- The primary endpoint is the percentage of patients with no suspected residual tumor on breast MRI and biopsy after 12 weeks of neoadjuvant treatment, confirmed by histological analysis of the surgical specimen (breast tumor and axillary lymph nodes), corresponding to ypT0/Tis ypN0 according to the AJCC 8th edition classification
Study Overview
Brief Summary
The primary objective of our prospective multicenter study is to evaluate the efficacy of a neoadjuvant chemotherapy protocol consisting of 4 cycles of CARBOPLATIN PACLITAXEL + PEMBROLIZUMAB administered over 12 weeks in patients with stage II triple‑negative breast cancer (TNBC) with TILs ≥ 30%.
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female aged over 18 years
- •Histologically and/or cytologically confirmed invasive triple‑negative breast adenocarcinoma (ER and PR <10%, HER2‑negative) on all tumor samples.
- •Stage II: T2‑T3N0M0 or T1‑T2N1M0
- •TILs ≥ 30% on initial biopsy (TILs assessed according to the 2014 International TILs Working Group recommendations)
- •Tumor material available
- •Performance status ≤ 1 (WHO).
- •No contraindication to neoadjuvant chemotherapy or pembrolizumab
- •Adequate bone marrow function, defined as follows (laboratory tests within 21 days prior to inclusion): Absolute neutrophil count ≥ 1500/μL (1.5×10⁹/L) Hemoglobin ≥ 10 g/dL Platelets ≥ 100,000/μL (100×10⁹/L)
- •An adequate serum level of potassium, magnesium, and calcium (> ULN)
- •Adequate hepatic function, defined as follows (laboratory tests within 21 days prior to inclusion): Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN if known Gilbert syndrome) AST (SGOT) ≤ 2 × ULN ALT (SGPT) ≤ 2 × ULN PAL ≤ 2.5 × ULN
- •Adequate renal function, defined as follows (laboratory tests within 21 days prior to inclusion): Creatinine ≤ 1.5 × ULN or estimated GFR (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 screening
- •Negative serum pregnancy test at screening (for women of childbearing potential)
- •Women of childbearing potential must agree to use a highly effective method of contraception during screening, throughout study treatment, and for at least 7 months after the last administration. It is strongly recommended that the male partner also use a condom with spermicide during this period
- •Affiliation to a social security system or beneficiary of such a system
- •Ability to communicate and understand the French language without difficulty
- •Signed informed consent
Exclusion Criteria
- •Metastatic disease at diagnosis
- •Subjects with an ongoing acute urinary tract infection, pre-existing hemorrhagic cystitis, or known urinary tract obstruction.
- •Subjects with known or suspected hypersensitivity, or a severe allergy to any of the active substances or excipients of the study drugs, such as lactose.
- •Prior use of systemic immunosuppressive drugs (except physiological replacement therapy) within 30 days before starting study treatment
- •Live attenuated vaccine administered within 30 days prior to the start of study treatment
- •Active infection, including: Tuberculosis (TB) Hepatitis B: positive HBsAg. Subjects with past/resolved HBV infection (anti‑HBc positive, HBsAg negative) are eligible. Hepatitis C: anti‑HCV positive subjects eligible only if HCV RNA PCR is negative. HIV infection: HIV‑positive subjects eligible if treated and with undetectable viral load
- •Significant cardiovascular disease (NYHA class II or higher), cardiomyopathy, acute inflammatory heart diseases, myocardial infarction, TIA or stroke within the past 3 months, unstable arrhythmias, or unstable angina
- •Participation in other studies involving one or more investigational medicinal products within the 3 weeks prior to 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 from other studies is permitted, provided that no procedures likely to interfere with the interpretation of the results of the present study are performed.
- •Uncontrolled medical, neuropsychiatric condition, or significant substance dependence that, in the investigator’s opinion, may interfere with study completion
- •Vulnerable individuals as defined by the French Public Health Code (L.1121‑6), or adults under legal protection/unable to provide informed consent (L.1121‑8)
- •Patient with recurrent breast cancer.
- •Bilateral breast cancer
- •Patients with current use of Millepertuis
- •Invasive breast adenocarcinoma with ER and PR >10% and/or HER2‑positive
- •Any other malignancy within the past 3 years, except for cancers considered adequately treated and at low risk of recurrence
- •Pregnant women, women who may become pregnant without effective contraception, or breastfeeding women
- •Patients with a contraindication to MRI
- •Diagnosis of immunodeficiency
- •Presence of an active autoimmune disease requiring systemic treatment within the past 3 years. Examples: inflammatory bowel disease, lupus, ankylosing spondylitis, scleroderma, multiple sclerosis, celiac disease, Wegener’s granulomatosis. Note: history of atopy, asthma, vitiligo, alopecia, Graves’ disease, Hashimoto’s thyroiditis, or psoriasis not requiring systemic therapy does not lead to exclusion. Replacement therapy (e.g., thyroxine, insulin, physiological corticosteroids) is not considered systemic treatment
- •Participants must not have received prior systemic therapy or curative-intent radiotherapy for the current breast cancer
Arms & Interventions
EPIRUBICINE MEDAC 2 mg/ml, solution pour perfusion
Test
Intervention: EPIRUBICINE MEDAC 2 mg/ml, solution pour perfusion (Drug)
KEYTRUDA 25 mg/mL concentrate for solution for infusion.
Test
Intervention: KEYTRUDA 25 mg/mL concentrate for solution for infusion. (Drug)
PACLITAXEL HOSPIRA 6 mg/mL, solution for dilution for infusion
Test
Intervention: PACLITAXEL HOSPIRA 6 mg/mL, solution for dilution for infusion (Drug)
CARBOPLATINE ACCORD 10 mg/ml, solution pour perfusion
Test
Intervention: CARBOPLATINE ACCORD 10 mg/ml, solution pour perfusion (Drug)
DOXORUBICINE ARROW 2 mg/ml, solution pour perfusion
Test
Intervention: DOXORUBICINE ARROW 2 mg/ml, solution pour perfusion (Drug)
Endoxan
Test
Intervention: Endoxan (Drug)
Outcomes
Primary Outcomes
The primary endpoint is the percentage of patients with no suspected residual tumor on breast MRI and biopsy after 12 weeks of neoadjuvant treatment, confirmed by histological analysis of the surgical specimen (breast tumor and axillary lymph nodes), corresponding to ypT0/Tis ypN0 according to the AJCC 8th edition classification
The primary endpoint is the percentage of patients with no suspected residual tumor on breast MRI and biopsy after 12 weeks of neoadjuvant treatment, confirmed by histological analysis of the surgical specimen (breast tumor and axillary lymph nodes), corresponding to ypT0/Tis ypN0 according to the AJCC 8th edition classification
Secondary Outcomes
- Event‑free survival (EFS), which will be calculated as the time from inclusion to the occurrence of one of the following events: disease progression preventing surgery, local or distant recurrence, second primary cancer (breast or other), or death from any cause
- Overall survival, which will be calculated from the date of inclusion to the date of death from any cause.
- Residual cancer burden (RCB), which 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 definition by Symmans et al. (28). RCB‑0 is defined as a 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
- Toxicity related to chemotherapy and immunotherapy, which will be assessed by the presence and grade of adverse events of interest related to chemotherapy and pembrolizumab immunotherapy
- Quality of life, which will be assessed using the EORTC QLQ‑C30 self‑questionnaire (at inclusion, before surgery, and 3 months after surgery) and the EQ‑5D‑5L (at each follow‑up visit for 3 years)
- Fear of recurrence, which will be assessed using the French version of the FCRI‑SF (Fear of Cancer Recurrence Inventory – Short Form) including 9 items, at inclusion, before surgery, and at each post‑treatment follow‑up visit for 3 years
- Complete response assessed on MRI, which will be compared with RCB‑0, RCB‑1, and RCB‑2‑3 rates
- The pre‑treatment TIL percentage (continuous and dichotomous variable) will be estimated and compared across RCB‑0, RCB‑1, and RCB‑2‑3 rates; TILs will be assessed according to the recommendations of the 2014 International TILs Working Group
- The exploratory endpoints are the identification and characterization of biomarkers through specific biological analyses including RNA expression profiling, spatial transcriptomic and proteomic analyses, and immunomonitoring
Investigators
SEGUIN LORENE
Scientific
Institut Paoli Calmettes
Study Sites (7)
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