Radiation Dose Intensity Study in Breast Cancer in Young Women

NCT ID: NCT00212121

Last Updated: 2022-01-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 2400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2025-12-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

low dose boost (16 Gy)

Group Type: ACTIVE_COMPARATOR

high dose boost

Intervention Type: RADIATION

high dose boost

boost

Intervention Type: PROCEDURE

low dose versus high dose

2

high boost (26 Gy)

Group Type: EXPERIMENTAL

high dose boost

Intervention Type: RADIATION

high dose boost

boost

Intervention Type: PROCEDURE

low dose versus high dose

Interventions

high dose boost

high dose boost

Intervention Type: RADIATION

boost

low dose versus high dose

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age 50 years or younger.
• Histological diagnosis of invasive mammary cancer including all subtypes of invasive adenocarcinoma.
• Tumor location and extension imaged prior to surgery using at least mammography and ultrasound.
• Unicentric tumors and multifocal tumors removed using a wide local excision; microscopic radical resection (focally involved margins allowed, defined as:

any DCIS or invasive carcinoma in 3 or fewer low-power fields (using a x 4 objective and a x 10 ocular lens, which has a diameter of 5 mm per low-power microscopic fields).

• Sentinel lymph node biopsy and/or axillary lymph node dissection has been performed.
• Breast cancer stage: pT1-2pN0-2a M0.
• No treatment is allowed prior to surgery (no neoadjuvant chemotherapy, no neoadjuvant hormonal therapy, no pre-operative radiotherapy).
• In cases where no adjuvant chemotherapy is given, wide local excision has been performed < 10 weeks before the start of radiotherapy.
• In cases where adjuvant chemotherapy is given immediately after surgery, wide local excision has been performed < 6 months before the start of radiotherapy, and chemotherapy should be completed < 6 weeks before the start of radiotherapy.
• In cases where hormonal treatment is planned, this is given after completion of the radiotherapy.
• No previous history or synchronous malignant tumor in the other breast, previous history of malignant disease, except adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
• ECOG performance scale 2 or less.

Exclusion Criteria

• Residual microcalcifications on mammogram.
• All histological types of malignancies other than invasive adenocarcinoma.
• In situ carcinoma of the breast, without invasive tumor.
• Concurrent pregnancy.
• Multicentric tumors, and multifocal. tumors excised using multiple excisions * Invasive breast cancer in both breasts.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Liesbeth Boersma, MD

Role: STUDY_CHAIR

MAASTRO Clinic, Heerlen

Locations

Hôpital J-Minjoz

Besançon, , France

Institut Bergonié

Bordeaux, , France

CHU Henri Mondor

Créteil, , France

Centre Oscar Lambret

Lille, , France

Institut Paoli Calmettes

Marseille, , France

Centre Val d'Aurelle

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

Institut Curie

Paris, , France

Hôpital Saint Louis

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Centre Eugène Marquis

Rennes, , France

Centre Henri Becquerel

Rouen, , France

Centre René Huguenin

Saint-Cloud, , France

Centre René Gauducheau

Saint-Herblain, , France

Centre Paul Strauss

Strasbourg, , France

CHU de Tours

Tours, , France

Institut Gustave Roussy

Villejuif, , France

The Netherlands Cancer Institute

Amsterdam, , Netherlands

Countries

France; Netherlands

Other Identifiers

2003-13

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

M03RBC-young boost

Identifier Type: -

Identifier Source: org_study_id