Single Fraction Preoperative Radiotherapy for Early Stage Breast Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Phase I; Radiation: Phase II

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 79
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Cristina Leonardi, MD; Phone Number: +39 02 57489037; Email: cristina.leonardi@ieo.it
• Study Contact Backup: Name: Anna Morra, MD; Phone Number: +39 02 57489037; Email: anna.morra@ieo.it

Study Locations

• Italy
  • Milan, Italy, 20141
    • Recruiting
    • IEO, European Institute of Oncology IRCCS
    • Contact: Maria Cristina Leonardi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Preoperative Radiation Treatment; Preoperative Radiation treatment with CyberKnife

Radiation: Phase I; 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.; Radiation: Phase II; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Principal Investigator: Maria Cristina Leonardi, European Institute of Oncology

Publications and helpful links

General Publications

• Zerella MA, Zaffaroni M, Ronci G, Dicuonzo S, Rojas DP, Morra A, Fodor C, Rondi E, Vigorito S, Botta F, Cremonesi M, Garibaldi C, Penco S, Galimberti VE, Intra M, Gandini S, Barberis M, Renne G, Cattani F, Veronesi P, Orecchia R, Jereczek-Fossa BA, Leonardi MC. Single fraction ablative preoperative radiation treatment for early-stage breast cancer: the CRYSTAL study - a phase I/II clinical trial protocol. BMC Cancer. 2022 Apr 2;22(1):358. doi: 10.1186/s12885-022-09305-w.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 5, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: radiosurgery; preoperative radiotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IEO 1308 - AIRC IG-23118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No