Hormonal Receptor (HR)-positive HER2 negative breast cancer patients treated with preoperative ELacestrant and PULSAR adaptive radiotherapy: a phase II study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Radioterapia Oncologica Onlus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Sep 2025 → ongoing

Decision date (initial)

2025-07-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Menarini Stemline

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess safety and tolerability of PULSAR preoperative radiation therapy and Elacestrant

Secondary objectives 2

1. Clinical efficacy as determined by response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) and Residual cancer burden (RCB)
2. Exploratory: Effect of PULSAR and Elacestrant on immuno- and biomarkers in tumor tissue and blood samples compared to pretreatment.

Conditions and MedDRA coding

Patients with HR-positive, HER2-negative, non-metastatic node positive BC eligible for neoadjuvant treatment (clinical stage II-III)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patients able to understand and follow instructions during the trial.
2. Patients with adequate renal function at Screening, confirmed at Baseline, defined by eGFR ≥ 30 mL/min using 2021 CKD-EPI creatinine equation.
3. Patients must be able to undergo CT/PET scan and MRI/Ultrasound imaging procedures for tumor diagnosis and follow-up.
4. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5. Life expectancy of at least 12 months according to the Investigator’s judgement.
6. Patients able and willing to give written informed consent, signed and dated.
7. Post-menopausal female and male patients.
8. Patients aged at least 18 years old at the time of ICF signature.
9. Any N-positive (stage II-III) HR+ HER2- breast cancer patients diagnosed as candidates for neoadjuvant chemotherapy
10. Patients with tumor accessible for biopsy and surgery
11. Patients with adequate bone marrow function at Screening, confirmed at Baseline, including: a. ANC ≥ 1.5 × 109/L; patients with documented benign cyclical neutropenia are eligible if white blood cell count is ≥ 1.5 × 109/L, with ANC ≥ 1.0 × 109/L, leukocytes ≥ 4.0 × 109/L, and lymphocytes ≥ 0.6 × 109/L; b. platelets ≥ 100 × 109/L; c. hemoglobin ≥ 9 g/dL (may have been transfused);
12. International Normalized Ratio (INR) < 1.5×Upper Limit of Normal (ULN); patients treated with vitamin K antagonist are eligible if INR < 3.
13. Patients with adequate hepatic function at Screening, confirmed at Baseline, defined by a. total bilirubin level ≤1.5×ULN; patients with documented Gilbert disease are allowed if total bilirubin ≤3×ULN; b. aspartate aminotransferase (AST) level ≤2.5×ULN, and alanine aminotransferase (ALT) level ≤2.5×ULN, or, for patients with documented metastatic disease to the liver, AST and ALT levels ≤5×ULN.
14. Measurable primary breast lesion ≥20mm at baseline breast MRI

Exclusion criteria 21

1. Patients with a history of any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, based on the Investigator’s judgement, provides a reasonable suspicion of a disease or condition that contraindicates the use of the PULSAR or Elacestrant or that might affect the interpretation of the trial results or render the patient at high risk for treatment complications.
2. Patients receiving any other treatment that, in the opinion of the Investigator, might interfere with the trial.
3. Patients with a current drug or substance abuse.
4. Patients with any significant co-morbidity which, according to the Investigator’s judgement, makes patient compliance to trial conditions unlikely.
5. Patients unable to understand the Protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial.
6. Patients who are unlikely to comply with the Protocol requirements, instructions and trialrelated restrictions, e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial.
7. Patients with legal incapacity or limited legal capacity.
8. Patients with any condition which results in an undue risk for the patient during the trial participation according to the Investigator.
9. Patients with previous malignant disease (other than the tumor disease for this trial) within the last five (5) years (except adequately treated non-melanoma skin cancers and carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least two (2) years prior to Screening, and the patient is deemed to have been cured with no additional therapy required or anticipated to be required.
10. Patients who underwent prior organ transplantation, including allogeneic stem cell transplantation.
11. Patients with history of uncontrolled intercurrent illness, including but not limited to uncontrolled hypertension (high blood pressure defined as BPD>=140 mmHg or BPS >=90 mmHg despite of combination therapy with diuretic/CCB/ACE or ARB).
12. Patients with active infection requiring systemic therapy with antibiotics (at both Screening and Baseline).
13. Patients with a known prior hypersensitivity or contraindications to any of the IMPs or any component in its formulations or any other drug scheduled or likely to be given during the trial
14. Patients with severe acute or chronic medical conditions, including a. Immune colitis b. Inflammatory bowel disease c. History of severe vomiting or diarrhea not having resolved to Grade 1 at Baseline d. Immune pneumonitis e. Pulmonary fibrosis f. Psychiatric conditions including recent (within the last year) or active suicidal ideation or behavior g. Laboratory abnormalities that may increase the risk associated with trial participation or trial treatment administration or may interfere with the interpretation of trial results and, in the judgement of the Investigator, would make the patient inappropriate for entry into this trial.
15. Patients with a history of small intestine resection surgery or other major gastrointestinal surgery that would preclude adequate absorption, distribution, metabolism, or excretion of Elacestrant.
16. Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at Screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody Screening test positive).
17. Patients with increased anesthesiological risk (e.g. known or predicted difficult airway) if general anesthetic is required.
18. Patients with increased bleeding risk (e.g. coagulopathies) and patients on anticoagulants.
19. Premenopausal state (defined as any woman who is not surgically sterile with a hysterectomy and/or bilateral oophorectomy or ≥ 12 months of amenorrhea and at least 50 years of age)
20. Patients who previously received Elacestrant or breast radiotherapy.
21. Patients participating in any other clinical trial within 30 days before Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Reported adverse events (AEs) and serious adverse events (SAEs)
2. Changes from Baseline in laboratory parameters (hematology, biochemistry, coagulation, and urinalysis), physical examinations, vital signs, and electrocardiograms (ECGs) during the Treatment and Follow-up periods.

Secondary endpoints 12

1. Tumor Pathological complete response (pCR), defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current American Joint Committee on Cancer (AJCC) system).
2. Residual cancer burden (RCB) as a determinant of the extent of residual disease in post-surgery. Six variables are included in the formula. An RCB index value can also be calculated and involves the categorization into one of four RCB classes (RCB 0 or pCR, RCB I or near pCR, RCB II, RCB III).
3. Event-free survival (EFS), defined as the time from first dose of PULSAR and Elacestrant to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause up to the end of the safety follow-up at 12 months.
4. Clinical efficacy based on available RECIST 1.1 assessments: Objective response rate (ORR): proportion of patients having a best overall response (BOR) of complete response (CR) or partial response (PR) relative to assessment at the Screening visit
5. Residual nodal burden (RNB)
6. Nodal pathologic complete response ([n]pCR) rate
7. Local Control (LC) rate
8. Overall Survival (OS), defined as time from the first PULSAR and Elacestrant administration to last follow up or death for any reason
9. Invasive disease-free survival (iDFS), defined as the time from first dose of PULSAR and Elacestrant until local or distant recurrence or death due to any cause up to the end of the safety follow-up at 12 month.
10. Exploratory: Metabolomic and transcriptomic assessment on tissue before (diagnostic biopsy) and after treatment (surgical specimen). Metabolomic will be performed in house using an LC-MS based approach using our new platform (LC-MS Agielnt Q-TOF 6546). Additional transcriptomic analysis will be performed.
11. Exploratory: Evaluation of the immune environment on tissue before (diagnostic biopsy) and after treatment (surgical specimen) (CD8, CD4, RBP-J CD163 and CD68 on immunohistochemistry).
12. Exploratory: ctDNA analysis on blood samples at baseline, 12 weeks from first PULSAR administration and at EoT visit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Radioterapia Oncologica Onlus

Sponsor organisation

Fondazione Radioterapia Oncologica Onlus

Address

Via Adelmo Santini 3

City

Agliana

Postcode

51031

Country

Italy

Scientific contact point

Organisation

Fondazione Radioterapia Oncologica Onlus

Contact name

Lorenzo Livi

Public contact point

Organisation

Fondazione Radioterapia Oncologica Onlus

Contact name

Gori Lorenzo

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications