Breast Cancer
Conditions
Keywords
preoperative radiotherapy, radiosurgery
Brief summary
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
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.
Interventions
RADIATIONPhase 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.
RADIATIONPhase 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.
Sponsors
European Institute of Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Identify the maximum tolerated dose (MTD) | time frame:2 weeks | 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). |
| Phase II: Evaluate efficacy measured in terms of pCR rate | time frame:8 weeks | Rate of pCR after radioablative treatment, according to Modified Residual Cancer Burden (RCB) index |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post surgery complications | time frame: within 30 days of surgery | Reporting of any post surgery complication (rate of infection, seroma, hematoma, necrosis, delayed wound healing) |
| Disease free survival | time frame: 1- 3 years | establish the rate of disease free survival |
| Incidence of chronic toxicity | time frame: 6 months - 3 years | Chronic skin/soft tissue, bone, lung and heart toxicities incidence measured according to NCI CTCAE v. 4.03 |
| Overall survival | time frame: 3 years | establish the rate of overall survival |
| Breast cancer specific survival | time frame: 3 years | establish the rate of breast cancer specific survival |
| Local relapse | time frame: 1 - 3 years | establish the rate of local relapse |
| Cosmetic outcomes | time frame: 1 - 3 years | Measured according to the 4 points scale (poor, fair, good, excellent) |
Countries
Italy
Contacts
Primary ContactMaria Cristina Leonardi, MD
Backup ContactAnna Morra, MD
Outcome results
None listed