Single Fraction Preoperative Radiotherapy for Early Stage Breast Cancer

Study Overview
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Brief Summary
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This is a phase I/II, single-arm and open-label single-centre clinical trial with the aim to test the feasibility, safety and the efficacy, in terms of complete pathological response, of preoperative ablative radiotherapy in single fraction for selected breast cancer patients.

Detailed Description
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The research plan is conceived in two sections, as follows. (i)The technical study handles the set-up, motion and dosimetric issues of the radioablation technique using CyberKnife system. (ii)The clinical section is organized in two studies: a phase I dose escalation study to identify the maximum tolerated dose (MTD) delivering 18 Gy, 21 Gy and 24 Gy in single fraction and a phase II study to evaluate the rate of pathological complete response (pCR) when a dose level is chosen according to the results of the previous phase I study. Study population includes patients affected by cT1-T2 (up to 2.5 cm) cN0, adenocarcinoma of the breast, diagnosed with conventional workup. Surgical tumor removal will be scheduled after 4-8 weeks after radioablation. Whole breast radiation therapy without boost will be performed after surgery.

Official Title
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Phase I/II Clinical Trial on Single Fraction Ablative Preoperative Radiation Treatment for Early Stage Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Phase I
* Radiation: Phase II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven unifocal adenocarcinoma T1-T2 Tumor size up to 2.5 cm cN0 Age ≥ 18 years old Good general condition (ECOG 0-2) Planned BCS Written informed consent Exclusion Criteria: Tumor close to skin or chest wall Pure non-invasive tumor Prior RT to the chest Neoadjuvant chemotherapy Collagenopathies Coagulation or autoimmunitary disorders Previous malignancies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preoperative Radiation Treatment<br> | Radiation: Phase I<br>* To establish the recommended dose defined as the maximum tolerated dose (MTD)The dose-limiting toxicity (DLT) is defined as any G3-G4 event according to NCI CTCAE Version 4.03 scale. Dose escalation is designed as a 3+3 rule-based study. Dose escalation will be initiated from a baseline dose of 18 Gy and increased to reach 21 Gy and 24 Gy. The population size includes 18 patients.<br>Radiation: Phase II<br>* The recommended dose from the phase I study is delivered, using Cyberknife in order to evaluate the efficacy measured in terms of pCR rate. The population size includes 61 patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Identify the maximum tolerated dose (MTD) | Dose escalation is designed as a 3+3 rule-based study. Acute skin/soft tissue toxicity, measured according to NCI CTCAE v. 4.03. Any Grade 3-4 toxicity related to radioablation is considered dose limiting (DLT). | time frame:2 weeks | 
| Phase II: Evaluate efficacy measured in terms of pCR rate | Rate of pCR after radioablative treatment, according to Modified Residual Cancer Burden (RCB) index | time frame:8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of chronic toxicity | Chronic skin/soft tissue, bone, lung and heart toxicities incidence measured according to NCI CTCAE v. 4.03 | time frame: 6 months - 3 years | 
| Cosmetic outcomes | Measured according to the 4 points scale (poor, fair, good, excellent) | time frame: 1 - 3 years | 
| Post surgery complications | Reporting of any post surgery complication (rate of infection, seroma, hematoma, necrosis, delayed wound healing) | time frame: within 30 days of surgery | 
| Disease free survival | establish the rate of disease free survival | time frame: 1- 3 years | 
| Local relapse | establish the rate of local relapse | time frame: 1 - 3 years | 
| Overall survival | establish the rate of overall survival | time frame: 3 years | 
| Breast cancer specific survival | establish the rate of breast cancer specific survival | time frame: 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preoperative radiotherapy, radiosurgery