Preoperative Immunotherapy Combined With Stereotactic Radiation Therapy Boost in the Treatment of HER2-negative Breast Cancer

NCT06472583 | Recruiting Phase 2 DMC

• 2 other identifiers: BREAST-BOOSTER2023-504145-31-00
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the study is to assess the safety and effectiveness of the combination of anti-PD1 immunotherapy (pembrolizumab) and radiotherapy in the preoperative treatment of HER2-negative breast cancer resistant to classical chemotherapy. The subject of the intervention will be:

1. 1.Randomly assigned in a 2:1 ratio and double-blinded addition of pre-operative immunotherapy with pembrolizumab or placebo to standard chemotherapy
2. 2.Addition of preoperative radiotherapy boost delivered with a CyberKnife radiosurgery system concomitantly with the use of paclitaxel (+/- carboplatin) and pembrolizumab / placebo.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• The histopathological confirmation of complete tumor regression in postoperative material performed in a population of 52 patients receiving immunotherapy in combination with radiotherapy

  The statistical analysis will be performed by comparison to the initial assumptions, according to Simon's scheme. The finding of complete tumor regression (confirmed histopathologically) in more than 11 patients out of the group of 52 enrolled will be treated as fulfillment of the primary endpoint.

  Rating histopathology of the collected material during surgery

Secondary Outcomes (5)

• Assessment of complete regression in postoperative histopathological examination in the population of all 78 patients receiving preoperative chemotherapy and radiotherapy

  Rating histopathology of the collected material during surgery

• The assessment of the response to preoperative treatment by assessing postoperative material in histopathological examination

  Rating histopathology of the collected material during surgery

• The comparison of the Invasive Disease Free Survival time the group treated with pembrolizumab with radiotherapy to the group treated with placebo with radiotherapy

  The entire observation period,an average of 4 years

• Quality of life evaluated by QLQ-C30 questionnaire (Quality of Live questionnaire) comparision beteewen groups

  Assessment approximately 4 months after surgical treatment

• Safety and tolerance (number of participants with treatment-related adverse events).

  During the study, an average of 5 years

Study Arms (2)

Experimental (Immunotherapy with pembrolizumab)

EXPERIMENTAL

Pembrolizumab (Keytruda) + Preoperative Stereotactic Radiotherapy. IP will administered at a dose of 200 mg by intravenous infusion every 21 days - 4 administrations planned.

Drug: Keytruda; Radiation: Preoperative radiation therapy

Control (placebo)

PLACEBO COMPARATOR

Placebo+ Preoperative Stereotactic Radiotherapy The solvent is 0.9% NaCl in a volume of 100 ml, with an adequate cover of the drug bag will be used as a placebo.

Radiation: Preoperative radiation therapy; Drug: Placebo

Interventions

Keytruda DRUG

Preoperative immunotherapy (200 mg, infusion every 21 days, 4 administrations planned)

Experimental (Immunotherapy with pembrolizumab)

Preoperative radiation therapy RADIATION

Boost of preoperative robotic stereotactic radiotherapy

Control (placebo); Experimental (Immunotherapy with pembrolizumab)

Placebo DRUG

0,9% NaCl in the volume 100 ml

Control (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A woman or a man over 18 years of age.
• Diagnosis of invasive breast cancer
• Patient eligible for standard preoperative chemotherapy for breast cancer with anthracyclines and paclitaxel, according to the investigator's assessment
• Breast cancer stage:
• any T cN1-cN3
• cT4 any N (stages IIA/IIB/III/IV, excluding cT1-3 N0 patients).
• Oligometastatic disease is allowed (stage IV, up to 3 foci in one organ or 2 foci in total in 2 different organs), 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 do not qualify for radical treatment cannot be included.
• Cancer without estrogen receptor expression (ER\<1% and PR\<1%) or luminal cancer
• HER2-negative cancer
• Definitely multifocal or multicentric tumors are acceptable if HER2 negative status is confirmed in all identified invasive tumor foci; this is not required in the case of satellite lesions adjacent to the tumor mass or small lesions less than 1 cm in diameter identified in MRI
• No prior chemotherapy for a current diagnosis of breast cancer and no prior anthracycline chemotherapy for any reason; earlier preoperative hormone therapy is allowed if, in the investigator's opinion, the patient requires the initiation of chemotherapy; patients may be included after 1 cycle of AC chemotherapy (1 administration) if the patient underwent a PET/CT (Positron Emission Tomography and Computed Tomography) scan using 18-FDG before starting treatment
• There are no contraindications to radiation treatment
• ECOG PS (Eastern Cooperative Oncology Group Performance Status) status 0 or 1
• Bone marrow function confirmed by hemoglobin concentration ≥9 g/dL and neutrophil count (ANC) ≥1500/μL and PLT (platelets) count ≥100,000/μL
• Bilirubin concentration ≤ 1.5 x upper limit of normal (ULN), except for patients with a diagnosis of Gilbert's syndrome confirmed by previous measurements or another method (then direct bilirubin ≤ ULN)

You may not qualify if:

• Inflammatory breast cancer (cT4d)
• Hypersensitivity to drugs or excipients used in the study, which, in the opinion of the researcher, does not allow therapy to be initiated
• Major surgical or medical procedure within 14 days prior to study entry; does not apply to ovariectomy performed laparoscopically, including as a risk-reducing surgical procedure and ovarian biopsy as a fertility preservation procedure and diagnostic procedures
• Parallel coexisting invasive cancer
• Co-existing known HIV (human immunodeficiency virus) infection, known active HBV (hepatitis B virus) or HCV (hepatitis C virus) 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 pembrolizumab therapy
• Any disease requiring systemic steroid therapy within 3 weeks before enrollment in the study
• Serious, uncontrolled mental illness
• Condition after organ allotransplantation
• Condition after implantation of devices that do not allow breast MRI examination (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
• 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,

Sponsors & Collaborators

• Maria Sklodowska-Curie National Research Institute of Oncology: lead

Study Sites (1)

Maria Sklodowska-Curie National Research Institute of Oncology , Gliwice Branch

Gliwice, Poland

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michal Jarzab

  Maria Sklodowska-Curie National Research Institute of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michal Jarzab

CONTACT

48322788716; michal.jarzab@gliwice.nio.gov.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: June 25, 2024
• Study Start: April 11, 2024
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2028
• Last Updated: June 25, 2024

Record last verified: 2024-04

Locations

PL (1)