A phase II study of preoperative stereotactic radiation therapy boost combined with short-course immunotherapy (pembrolizumab versus placebo, randomized, double-blind) and standard chemotherapy in patients with newly diagnosed HER2-negative non-metastatic breast cancer with lack of early metabolic response in 18-fluorodeoxyglucoseFDG-PET/CT after 1st chemoterapy cycle

Phase 1

Recruiting

• Conditions: HER2 negative breast cancer; MedDRA version: 23.0Level: PTClassification code: 10083232Term: HER2 negative breast cancer Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-504145-31-00
• Lead Sponsor: arodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-28
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

Woman or man over 18 years of age at the time of signing the informed consent for the study, No contraindications to radiation treatment, including those related to the diagnosis of a systemic disease (e.g. scleroderma), previous radiotherapy in the area covered by the planned irradiation, significant limitation of mobility, or the presence of implantable devices in the irradiated area; patients with a pacemaker/cardioverter can be treated if it is possible to safely perform radiotherapy procedures under the supervision of a cardiologist (confirmed by consultation), ECOG PS performance status 0 or 1, Bone marrow function confirmed by hemoglobin concentration =9 g/dL and neutrophil count (ANC) =1500/µL and platelet count =100,000/µL, Bilirubin concentration = 1.5 x upper limit of normal (ULN), except in patients with a confirmed diagnosis of Gilbert's syndrome by previous measurements or other method (then direct bilirubin = ULN), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 3 x ULN, Creatinine level = ULN or creatinine clearance =50 mL/min according to the Cockcroft-Gault method in patients with a creatinine level above the upper limit of normal, Left ventricular ejection fraction EF = 50%, No contraindications for breast magnetic resonance imaging (MR), In patients with procreative ability: consent to the implementation of adequate methods of contraception before inclusion in the study, during therapy and for at least 12 months after the end of systemic treatment (women) or 14 weeks (men), Giving informed written consent to participate in the study, Diagnosis of invasive breast cancer, Patient eligible for standard preoperative breast cancer chemotherapy with anthracyclines and paclitaxel, as assessed by the investigator, Breast cancer stage: any T at least cN1-cN3 or cT4 any N (stages IIAB-III, excluding patients cT1-3 N0). Oligometastatic disease (grade IV, up to 3 foci in one organ or 2 foci in 2 different organs in total) is acceptable, if radical treatment using local methods is possible, both in the treatment of the primary tumor and in the treatment of the metastatic focus (radiotherapy, surgery). Patients with distant metastases who are not eligible for radical treatment cannot be included, Triple negative estrogen receptor negative tumor (ER<1% and PR<1%) or HER2-negative luminal tumor. In postmenopausal patients with luminal A tumors (ER>30%, Ki67 below 20% and PR>30%), in postmenopausal patients no decrease in Ki67 to below 10% after 2-6 weeks of induction preoperative antihormonal therapy, HER2-negative tumor (expression assessed as 0 or + by immunohistochemistry, ++ expression negative by in situ hybridization assessment of HER2 amplification), Clearly multifocal or multicenter tumors are acceptable if the HER2-negative status is confirmed in all identified foci of invasive neoplasm; it is not required in the case of satellite foci adjacent to the tumor mass or small foci less than 1 cm in diameter, identified in an MRI examination, No prior chemotherapy due to a current diagnosis of breast cancer and no prior anthracycline chemotherapy for any reason; earlier preoperative hormone therapy is allowed if the patient, in the opinion of the investigator, requires chemotherapy; it is allowed to include patients after 1 module of AC chemotherapy (4 cycles), if the patient has performed a PET/CT scan with the use of 18-FDG before starting treatment, Oncological treatment for another cancer is acceptable i

Exclusion Criteria

Inflammatory breast cancer (cT4d), Condition after implantation of devices that do not allow MRI of the breast (does not apply to examinations with the assistance of a cardiologist, if the patient qualifies for such a procedure), Pregnancy or breastfeeding, Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 or drugs targeting other T cell receptor inhibitors (e.g. CTLA-4, OX-40, CD-137), History of non-infectious pneumonia requiring steroid therapy or current pneumonia, Active infection requiring systemic treatment, Significant cardiovascular disease, such as: acute coronary syndrome within the last 6 months, New York Heart Association (NYHA) class II-IV heart failure, or history of heart failure class III or IV, History of active tuberculosis, Other criteria, coexisting medical conditions, conditions, therapies, deviations in laboratory tests, or circumstances that, in the opinion of the investigator, do not allow the safe conduct of study procedures, may interfere with study results, or may substantially limit patient compliance with study rules, Hypersensitivity to drugs or auxiliary substances used in the study, in the opinion of the researcher, not allowing for therapy, Major surgical or medical procedure within 14 days prior to study entry; does not apply to risk-reducing surgery and diagnostic procedures, Parallel coexisting invasive cancer, Concomitant known HIV infection, known active HBV or HCV infection, Diagnosed autoimmune disease requiring immunosuppressive therapy; does not apply to thyroid diseases, if in the opinion of the endocrinologist they are not a contraindication to starting pembrolizumab therapy, Any disease requiring systemic steroid therapy within 3 weeks prior to study entry, Serious, uncontrolled mental illness, Condition after organ allotransplantation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified