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Radiation Dose Intensity Study in Breast Cancer in Young Women

Phase 3
Active, not recruiting
Conditions
Breast Cancer
Interventions
Radiation: high dose boost
Procedure: boost
Registration Number
NCT00212121
Lead Sponsor
The Netherlands Cancer Institute
Brief Summary

hypothesis: 10 Gy additional boost to the tumor bed will yield an increase in local control at 10 years from 88% to 93%, with still acceptable cosmesis.

Detailed Description

Title of the study:

Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed.

Background and aim of the study:

Several studies showed that breast conserving therapy (BCT) yields similar survival rates as mastectomy. BCT consists of lumpectomy followed by whole breast radiotherapy (WBRT). Three studies showed that an additional dose to the tumor bed, after 50 Gy WBRT, reduces the local recurrence rate (LRR). The largest of these 3 studies was a recent EORTC trial, which also showed that young age was an independent risk factor for LR after BCT.

In patients \< 51 years of age, the LR rate was reduced with 50% after a 66 Gy dose to the tumor bed, compared to 50 Gy (5-year LRR 12% vs 5.9%, p \< 0.02). However, the LRR in young women was still quite high (\> 1% per year). Therefore the first aim of the study is to investigate whether an additional boost dose to the tumorbed (26 Gy) reduces the LRR further. Therefore, we will compare the effect of a low boost dose (16 Gy) with the effect of a high boost dose (26 Gy) on the LRR, but also on the cosmetic outcome.

The second, very important aim of this study is to investigate whether we can find genetic or protein profiles that correlate with LRR, lymph node metastases, distant metastases, survival, radiosensitivity, and age. For this purpose we will obtain frozen tumor material and blood samples of as many patients as possible.

Population, study design, intervention:

Patients younger than 51 years of age, with stage T1-2N01-2aM0 breast cancer, and where the tumor can be locally excised with acceptable cosmetic result, will be randomized between a 16 Gy boost dose to the tumorbed and a 26 Gy boost dose to the tumor bed, after 50 Gy WBRT. Patients will be stratified based on age, tumor size, lymph node metastases, estrogen receptor status, interstitial or external boost irradiation, and institution. In principle frozen tumor samples and blood samples will be stored of each patient.

Endpoints and statistics:

The primary endpoint is LRR are 10 years. The secondary endpoint is cosmetic result, which will be quantified using digitized color photographs. In addition, patients will be asked to give their opinion about the cosmetic result using standardized questionnaires.

To find an increase in the local control rate of 88% to 93% at 10 year, with a power of 80% and a significance level of 5%, 580 patients will be included in each treatment arm.

Side studies:

An extremely important aspect of this trial is to obtain fresh tumor material and blood samples. These will be used to determine genetic and protein profiles aimed at finding subgroups based on these profiles, which may take more or less advantage of the additional radiation treatment.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
2400
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1boostlow dose boost (16 Gy)
2high dose boosthigh boost (26 Gy)
2boosthigh boost (26 Gy)
1high dose boostlow dose boost (16 Gy)
Primary Outcome Measures
NameTimeMethod
Local control at 10 yrat every follow up visit (< 2 months after last radiation treatment and thereafter yearly
Secondary Outcome Measures
NameTimeMethod
Cosmetic outcomeprior to radiotherapy, 1 year after radiotherapy and thereafter every 3 years

Trial Locations

Locations (18)

Hôpital J-Minjoz

🇫🇷

Besancon, France

Centre Oscar Lambret

🇫🇷

Lille, France

Institut Bergonié

🇫🇷

Bordeaux, France

CHU Henri Mondor

🇫🇷

Creteil, France

Institut Paoli Calmettes

🇫🇷

Marseille, France

Centre Val d'Aurelle

🇫🇷

Montpellier cedex 5, France

Institut Curie

🇫🇷

Paris, France

Centre Antoine Lacassagne

🇫🇷

Nice, France

Hôpital Saint Louis

🇫🇷

Paris, France

Centre Eugène Marquis

🇫🇷

Rennes, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre Benite Cedex, France

Centre Henri Becquerel

🇫🇷

Rouen, France

Centre René Huguenin

🇫🇷

Saint Cloud, France

Centre René Gauducheau

🇫🇷

Saint Herblain Cedex, France

Centre Paul Strauss

🇫🇷

Strasbourg, France

CHU de Tours

🇫🇷

Tours, France

Institut Gustave Roussy

🇫🇷

Villejuif, France

The Netherlands Cancer Institute

🇳🇱

Amsterdam, Netherlands

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