Breast CancerPhase 2BREAST-BOOSTERNCT06472583
Preoperative Immunotherapy Combined With Stereotactic Radiation Therapy Boost in the Treatment of HER2-negative Breast Cancer
A Phase 2 study testing Keytruda and Preoperative radiation therapy in people with Breast Cancer, run by Maria Sklodowska-Curie National Research Institute of Oncology at 1 site in Poland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Keytruda and Preoperative radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 sitePoland
- Study dates
- 11 Apr 2024to 28 Feb 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Show all 22Show fewer
- 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
- Any oncological treatment for another cancer is acceptable if it was radical, ended at least 1 year before inclusion in the study and did not include radiotherapy in the chest area on the same side as the currently treated breast cancer
- 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)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity ≤ 3 x ULN
- Creatinine concentration ≤ ULN or creatinine clearance ≥50 mL/min according to the Cockcroft-Gault method in patients with creatinine concentration above the upper limit of normal
- Left ventricular ejection fraction EF ≥ 50%
- No contraindications to breast magnetic resonance imaging (MRI)
- In patients with reproductive potential: consent to implement adequate contraceptive methods before enrollment in the study, during therapy and for at least 6 months after the end of systemic treatment
- Giving informed written consent to participate in the study
Who cannot join
- 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
Show all 17Show fewer
- 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,
- History of active tuberculosis
- Other criteria, comorbidities, conditions, therapies, laboratory abnormalities, or circumstances that, in the investigator's opinion, do not allow the study procedures to be safely performed, may interfere with the study results, or may substantially impair patient compliance
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Poland1 site, 1 recruiting
- Recruiting
Maria Sklodowska-Curie National Research Institute of Oncology , Gliwice Branch
Gliwice
Michal Jarzab
About this study
Official title: A Phase II Study of Preoperative Stereotactic Radiation Therapy Boost Combined With Short-course Immunotherapy (Pembrolizumab Versus Placebo, Randomized, Double-blind) and Standard Chemiotherapy in Patients With Newly Diagnosed HER2-negative Nonmetastatic Breast Cancer With Lack of Early Metabolic Response in 18- fluorodeoxyglucoseFDG-PET/CT After 1st Chemoterapy Cycle
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:
- Randomly assigned in a 2:1 ratio and double-blinded addition of pre-operative immunotherapy with pembrolizumab or placebo to standard chemotherapy
- Addition of preoperative radiotherapy boost delivered with a CyberKnife radiosurgery system concomitantly with the use of paclitaxel (+/- carboplatin) and pembrolizumab / placebo.
Read the detailed description
The study aims to assess the safety and effectiveness of the combination of anti-PD1 (PD-1, programmed cell death-1) immunotherapy (pembrolizumab) with radiotherapy in the preoperative treatment of triple-negative or luminal HER2-negative (HER2, Human epidermal growth factor receptor 2) (breast cancer, stage IIA/IIB/III/IV (with an acceptable oligometastatic form), resistant to classical chemotherapy
After screening and administration of standard induction chemotherapy, the study will be conducted in a group of patients selected on the basis of lack of metabolic response after the 1st cycle of chemotherapy, and the subject of the intervention will be:
- addition of preoperative immunotherapy with pembrolizumab or placebo to standard chemotherapy, using a double-blind randomized trial in a ratio of 2:1, respectively
- addition of a boost of preoperative robotic stereotactic radiotherapy in all patients, simultaneously with the use of paclitaxel +/- carboplatin and pembrolizumab/placebo.
- Conditions
- Breast Cancer
- Being tested
- Keytruda, Preoperative radiation therapy, Placebo
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KeytrudaDrug
Preoperative immunotherapy (200 mg, infusion every 21 days, 4 administrations planned)
Preoperative radiation therapyRadiation
Boost of preoperative robotic stereotactic radiotherapy
PlaceboDrug
0,9% NaCl in the volume 100 ml
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Radiation: Preoperative radiation therapy; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The finding of of complete tumor regression in more than 13 patients out of the group of 78 included and receiving both chemotherapy and radiotherapy will be treated as fulfillment of the secondary endpoint criterion.
Measured: Rating histopathology of the collected material during surgery
The assessment of the response to preoperative treatment by assessing postoperative material in histopathological examination
Assessment of regression under the influence of pembrolizumab in postoperative histopathological examination using the quantitative method, taking into account the degree of partial regression
Measured: 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
Invasive Disease Free Survival time will be evaluated according to Proposal for Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials
Measured: The entire observation period,an average of 4 years
Quality of life evaluated by QLQ-C30 questionnaire (Quality of Live questionnaire) comparision beteewen groups
General health condition based on the QLQ-C30 scale
Measured: Assessment approximately 4 months after surgical treatment
Safety and tolerance (number of participants with treatment-related adverse events).
Assessment of safety and tolerance of treatment according to Common Terminology Criteria for Adverse Events v. 5.0;
Measured: During the study, an average of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2024
- Study start11 Apr 2024
- Primary completion28 Feb 2028 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maria Sklodowska-Curie National Research Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michal Jarzab, Principal investigator, Maria Sklodowska-Curie National Research Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06472583
- Sponsor's protocol ID
- BREAST-BOOSTER
- Other IDs
- 2023-504145-31-00, 2023
- Acronym
- BREAST-BOOSTER
- Status last verified
- Apr 2024
- First submitted
- 21 May 2024
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Preoperative Stereotactic Radiation Therapy Boost Combined With Short-course Immunotherapy (Pembrolizumab Versus Placebo, Randomized, Double-blind) and Standard Chemiotherapy in Patients With Newly Diagnosed HER2-negative Nonmetastatic Breast Cancer With Lack of Early Metabolic Response in 18- fluorodeoxyglucoseFDG-PET/CT After 1st Chemoterapy Cycle
- ClinicalTrials.gov ID
- NCT06472583
- Acronym / sponsor ID
- BREAST-BOOSTER / BREAST-BOOSTER
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Maria Sklodowska-Curie National Research Institute of OncologyUniversity, hospital or other
- Study start
- 11 Apr 2024 (actual)
- Primary completion
- 28 Feb 2028 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 25 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Randomly assigned in a 2:1 ratio and double-blinded addition of pre-operative immunotherapy with pembrolizumab or placebo to standard chemotherapy
- Addition of preoperative radiotherapy boost delivered with a CyberKnife radiosurgery system concomitantly with the use of paclitaxel (+/- carboplatin) and pembrolizumab / placebo.
Detailed description
The study aims to assess the safety and effectiveness of the combination of anti-PD1 (PD-1, programmed cell death-1) immunotherapy (pembrolizumab) with radiotherapy in the preoperative treatment of triple-negative or luminal HER2-negative (HER2, Human epidermal growth factor receptor 2) (breast cancer, stage IIA/IIB/III/IV (with an acceptable oligometastatic form), resistant to classical chemotherapy
After screening and administration of standard induction chemotherapy, the study will be conducted in a group of patients selected on the basis of lack of metabolic response after the 1st cycle of chemotherapy, and the subject of the intervention will be:
- addition of preoperative immunotherapy with pembrolizumab or placebo to standard chemotherapy, using a double-blind randomized trial in a ratio of 2:1, respectively
- addition of a boost of preoperative robotic stereotactic radiotherapy in all patients, simultaneously with the use of paclitaxel +/- carboplatin and pembrolizumab/placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental (Immunotherapy with pembrolizumab) | Experimental | Drug: Keytruda, Radiation: Preoperative radiation therapyPembrolizumab (Keytruda) + Preoperative Stereotactic Radiotherapy. IP will administered at a dose of 200 mg by intravenous infusion every 21 days - 4 administrations planned. |
| Control (placebo) | Placebo comparator | Radiation: Preoperative radiation therapy, Drug: PlaceboPlacebo+ 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- Cancer without estrogen receptor expression (ER<1% and PR<1%) or luminal cancer
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KeytrudaPreoperative immunotherapy (200 mg, infusion every 21 days, 4 administrations planned) | Drug | Experimental (Immunotherapy with pembrolizumab) |
| Preoperative radiation therapyBoost of preoperative robotic stereotactic radiotherapy | Radiation | Control (placebo), Experimental (Immunotherapy with pembrolizumab) |
| Placebo0,9% NaCl in the volume 100 ml | Drug | Control (placebo) |
Primary outcome
The histopathological confirmation of complete tumor regression in postoperative material performed in a population of 52 patients receiving immunotherapy in combination with radiotherapy
Time frame: Rating histopathology of the collected material during surgery
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.
5 secondary outcomes
Assessment of complete regression in postoperative histopathological examination in the population of all 78 patients receiving preoperative chemotherapy and radiotherapy
Time frame: Rating histopathology of the collected material during surgery
The assessment of the response to preoperative treatment by assessing postoperative material in histopathological examination
Time frame: 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
Time frame: The entire observation period,an average of 4 years
Quality of life evaluated by QLQ-C30 questionnaire (Quality of Live questionnaire) comparision beteewen groups
Time frame: Assessment approximately 4 months after surgical treatment
Safety and tolerance (number of participants with treatment-related adverse events).
Time frame: During the study, an average of 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michal Jarzab principal investigator
Maria Sklodowska-Curie National Research Institute of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Keytruda and Preoperative radiation therapy in people with Breast Cancer, run by Maria Sklodowska-Curie National Research Institute of Oncology at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michal Jarzab (48322788716, michal.jarzab@gliwice.nio.gov.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The histopathological confirmation of complete tumor regression in postoperative material performed in a population of 52 patients receiving immunotherapy in combination with radiotherapy (time frame: Rating histopathology of the collected material during surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.