Hormonal Receptor (HR)-Positive HER2 Negative Breast Cancer Patients Treated With Preoperative ELacestrant and PULSAR Radiotherapy

NCT07005882 | Not Yet Recruiting Phase 2

• 2 other identifiers: HELP Trial2025-520762-22-00
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof-of-concept phase II trial to assess the safety (as primary endpoint) and clinical efficacy of neoadjuvant therapy with Elacestrant and PULSAR. The study will enroll 21 postmenopausal patients with early HR+ HER2- node positive BC, clinically staged II-III. Patients will receive Elacestrant 345 mg orally once daily for 24 weeks and PULSAR on the MRI-based breast gross tumor volume (GTVt), consisting of 10 Gy "pulse" every 4 weeks for a maximum of 5 or less in case of radiologic complete response. Surgery will be planned 24 weeks after Elacestrant initiation and at least 2 weeks from the last pulse and will be performed as per recommended clinical practice. Patients will then receive adjuvant systemic therapy as per standard of care and postoperative RT to the locoregional lymph nodes in case of nodal residual disease, if indicated.

Conditions

Breast Cancer Patients; Breast Cancer Early Stage Breast Cancer (Stage 1-3); HR+/HER2- Breast Cancer; Radiation Therapy

Outcome Measures

Primary Outcomes (9)

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of reported adverse events (AEs) and serious adverse events (SAEs), according to CTCAE v5.0. Evaluation of changes from Baseline during the Treatment and Follow-up periods.

  Baseline, every two weeks in the pre-operative period, 30 days and 3 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- laboratory parameters: hematology (Hemoglobin, HMCV, MCH, MCHC, RBC, WBC with differential count, and platelet count); biochemistry (Sodium, potassium, calcium, chloride, glucose (fasting), anorganic phosphate, cholesterol, triglycerides, total protein, uric acid, urea, creatinine, total bilirubin, alkaline phosphatase, ALT, AST, gamma-GT, LDH, CPK, amylase, and lipase); coagulation (PT, INR and activated partial thromboplastin time); and urinalysis (Leukocytes, nitrite, pH, protein, glucose, ketone, urobilinogen, bilirubin, hemoglobin, erythrocytes, specific gravity.). These values will be used to assess the patient's health status and the presence of any adverse events that may have arisen after therapy.

  Baseline, every two weeks unitl week 4, then every 4 weeks in the pre-operative period, 30 days and 3 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- physical examinations: (i.e. ECOG PS 0-5).

  Baseline, every two weeks in the pre-operative period, 30 days, 3 months, 6 months and 12 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- vital signs: temperature in °C

  Baseline, every two weeks until week 4 and then every 4 weeks in the pre-operative period, 30 days, 3 months, 6 months and 12 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- electrocardiograms: heart rate, PR/PQ interval, QRS interval, QT interval.

  Baseline, at the beginning (week 0) and at the end (week 20) of pre-operative treatment.

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- vital signs: heart rate in beats/min (bpm).

  Baseline, every two weeks until week 4 and then every 4 weeks in the pre-operative period, 30 days, 3 months, 6 months and 12 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- vital signs: blood pressure in mmHg.

  Baseline, every two weeks until week 4 and then every 4 weeks in the pre-operative period, 30 days, 3 months, 6 months and 12 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- vital signs: respiratory frequency in breaths/min.

  Baseline, every two weeks until week 4 and then every 4 weeks in the pre-operative period, 30 days, 3 months, 6 months and 12 months after surgery

• Safety of Elacestrant combined with PULSAR radiation therapy in preoperative setting

  Evaluation of changes from Baseline during the Treatment and Follow-up periods in: \- vital signs: SpO2 in %.

  Baseline, every two weeks until week 4 and then every 4 weeks in the pre-operative period, 30 days, 3 months, 6 months and 12 months after surgery

Study Arms (1)

Preoperative Elacestrant+PULSAR

EXPERIMENTAL

Drug: Elacestrant; Radiation: PULSAR

Interventions

Elacestrant DRUG

Preoperative treatment

Preoperative Elacestrant+PULSAR

PULSAR RADIATION

Preoperative treatment

Preoperative Elacestrant+PULSAR

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven HR-positive, HER2-negative BC
• Clinical disease stage II-III
• Post-menopausal female patients or male patients
• Eligible for neoadjuvant treatment and subsequent surgery
• No contraindication to MRI
• Patient able to understand and follow instructions during the trial
• Patient able and willing to give written informed consent, signed and dated
• Patient aged at least 50 years old
• Patient with tumor accessible for biopsy and surgery
• Patient with adequate bone marrow function at Screening, confirmed at Baseline, including:
• 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;
• platelets ≥ 100 × 109/L;
• hemoglobin ≥ 9 g/dL (may have been transfused);
• International Normalized Ratio (INR) \< 1.5×Upper Limit of Normal (ULN); patients treated with vitamin K antagonist are eligible if INR \< 3
• Patient with adequate hepatic function at Screening, confirmed at Baseline, defined by:

You may not qualify if:

• \. Patients with stage IV disease 2. 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 RT and/or Elacestrant or that might affect the interpretation of the trial results or render the patient at high risk for treatment complications.
• \. Patients with any significant co-morbidity which, according to the Investigator's judgement, makes patient compliance to trial conditions unlikely.
• \. 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.
• \. Patients with a history of uncontrolled intercurrent illness. 6. Patients with a known prior hypersensitivity or contraindications to Elacestrant or any component in its formulations.
• \. Patients with severe acute or chronic medical conditions, including:
• Immune colitis
• Inflammatory bowel disease
• History of severe vomiting or diarrhea not having resolved to Grade 1 at Baseline
• Immune pneumonitis
• Pulmonary fibrosis
• Psychiatric conditions including recent (within the last year) or active suicidal ideation or behavior
• 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.
• \. Patients with a history of small intestine resection surgery or other major gastrointestinal surgery.
• \. Patients with an active infection requiring systemic therapy with antibiotics (at both Screening and Baseline).
• \. Patients with a known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome or multi-drug-resistant gram-negative bacteria.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead

Study Sites (1)

AOU Careggi Radiation Oncology Unit

Florence, 50134, Italy

Location

MeSH Terms

Interventions

elacestrant; DEAE-Dextran

Intervention Hierarchy (Ancestors)

Dextrans; Glucans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: June 5, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: June 5, 2025

Record last verified: 2025-03

Locations

IT (1)