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Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast (ROMANCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03878342
Recruitment Status : Recruiting
First Posted : March 18, 2019
Last Update Posted : July 28, 2020
National Cancer Institute, France
Information provided by (Responsible Party):

Brief Summary:

Following breast-conserving surgery (BCS) for localized ductal carcinoma in situ (DCIS) of the breast, whole-breast irradiation (WBRT) is a standard of care, reducing the absolute rate of in-breast recurrences (IBR) by more than 15% at 10 years, from 28% without radiotherapy to 13 % with radiotherapy. Half of the recurrences occurred as invasive disease. Whereas in the comparative trials, WBRT did not impact on overall survival, survival of patients who recurred with invasive cancers was impaired in comparison to patients who did not recur, or to patients with DCIS-only recurrences.

Using criteria based on age, tumor size, nuclear grade, and margins status, several trials and cohort studies failed to identify subgroups of patients at low risk, who could be safely spared the need for WBRT. The Radiation Therapy Oncology Group (RTOG) DCIS trial included patients treated with BCS for low- or intermediate grade DCIS revealed by unifocal microcalcifications, size ≤25 mm, margins ≥3 mm, and no residual microcalcifications after surgery. The 5-year rates of IBR were 3.5 % without radiotherapy, versus 0.4 % with radiotherapy, and 6.7 % and 0.9 % at 7 years, respectively (p <0.001). Sixty percent of the patients received tamoxifen in both groups.

Several studies showed that the same molecular classes were identified in DCIS as in invasive cancers. Studies suggested that low proliferation, hormone receptors expression, and lack of ERBB2 amplification were associated with a low risk of IBR in patients not receiving radiotherapy. A combined signature was tested in the Eastern Cooperative Oncology Group (ECOG) trial, showing a 10% IBR rate at ten years in patients with a low-risk.

Identifying very low-risk DCIS, using biological markers in addition to the clinical and histological markers of low-risk DCIS, could help to select patients who could be safely avoided WBRT following BCS. It would avoid over-treatment in these women and could decrease the cost of management.

Condition or disease Intervention/treatment Phase
DCIS Breast Cancer Low Risk DCIS Breast Conserving Surgery Radiotherapy Omission Radiation: Radiotherapy Other: No Radiotherapy Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 666 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Prospective Study of Omission of Whole-breast Radiotherapy Following Breast-conserving Surgery in Patients With Very Low Risk Ductal Carcinoma in Situ of the Breast
Actual Study Start Date : May 10, 2019
Estimated Primary Completion Date : June 27, 2027
Estimated Study Completion Date : July 27, 2032

Arm Intervention/treatment
Active Comparator: Radiotherapy
two fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines
Radiation: Radiotherapy
two fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines

Experimental: No Radiotherapy
No Irradiation- Active surveillance
Other: No Radiotherapy
No Irradiation- Active surveillance

Primary Outcome Measures :
  1. 5-year cumulative incidence of in-breast cancer recurrences [ Time Frame: 5 years ]
    Incidence of breast recurrence is determined from the date of last surgery to the date of breast recurrence.

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 10 years ]
    OS is defined as the interval between the date of last surgery and the date of death from any cause;

  2. Breast cancer-specific survival (BCSS) [ Time Frame: 10 years ]
    BCSS is defined as the interval between the date of last surgery and the date of death from breast cancer

  3. Relapse-free survival (RFS) [ Time Frame: 10 years ]
    RFS is defined as the interval between the date of last surgery and the date of ipsilateral breast recurrence, regional nodes recurrence, distant metastases, of death from breast cancer, whichever occurs first

  4. Rate of in-breast recurrences (IBR). [ Time Frame: 10 years ]
    In-breast recurrence defined as any carcinoma (invasive or in situ) occurring in the treated breast

  5. Rate of Contralateral breast [ Time Frame: 10 years ]
    Contralateral breast cancer defined as any carcinoma (invasive or in situ) occurring in the contralateral breast.

  6. Quality of life of the patients using EORTC-QLQ-C 30 [ Time Frame: 3 years ]
    Quality of life will be assessed using QLQ-C 30 questionnaire from the European Organization for Research and Treatment of Cancer (EORTC). It is a 30-item self-reporting questionnaire developed to assess the quality of life of cancer patients. It is grouped into five functional subscales (role, physical, cognitive, emotional and social functioning). In addition, there are three multi-item symptom scales (fatigue, pain, and nausea and vomiting), individual questions concerning common symptoms in cancer patients,and two questions assessing overall Quality of Life

  7. Quality of life of the patients using EORTC-QLQ-BR23 [ Time Frame: 3 years ]
    Quality of Life of Patients will be assessed using a EORTC-QLQ BR23.It is a 23-item self-reporting specific questionnaire developed to assess the quality of life of breast cancer patients. It permits to evaluate the symptoms of breast cancer and the side effects of treatment.

  8. Cosmetics Evaluation [ Time Frame: 3 years ]
    cosmetic results will be evaluated by centralized photographic analysis.

Information from the National Library of Medicine

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Ages Eligible for Study:   51 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Woman aged >50 years,
  2. Postmenopausal Status; Note: Note: woman is considered post-menopausal if she has had amenorrhea for 12 months or more or has undergone surgical oophorectomy.
  3. ECOG performance status ≤2
  4. Microcalcifications on pre-operative mammography, unifocal, ≤25 mm;
  5. Absence of residual microcalcifications on post-operative mammography;
  6. Breast-conserving surgical excision;
  7. Histologically proven DCIS of the breast without an invasive component; Note: histological finding of DCIS lesions associated with or developed in a benign breast lesion or in case of a classical lobular carcinoma in situ (LCIS) associated with the DCIS are accepted.
  8. Free margins (≥2 mm), or free margins following re-excision;
  9. Low or Intermediate nuclear grade; Note: In case of nuclear grade heterogeneity, the higher -grade score will prevail.
  10. Tumour tissue sample availability; Note: Surgical specimen is mandatory unless no residual disease on the surgical specimen. In this instance, the initial diagnosis biopsy is required.
  11. Absence of extensive necrosis;
  12. Immunohistochemical characteristics of luminal A subtype: estrogen receptor (ER) ≥10 %, progesterone receptor (PR) ≥20 %, human epidermal growth factor receptor-2 (HER2) negative (0/1+) or 2+ not amplified (confirmed by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)), Ki67 <15%.
  13. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations and including follow-up;
  14. Written informed consent;
  15. Affiliation to the French social security.

Exclusion Criteria:

  1. Endocrine treatment for breast cancer;
  2. Previous diagnosis of DCIS or invasive cancer, (except basal-cell, carcinoma in situ of the cervix or endometrium);
  3. Synchronous bilateral DCIS;
  4. Known breast-cancer predisposing germ-cell mutation;
  5. Palpable tumour opacity or bloody nipple discharge;
  6. Histological evidence of multifocality (defined as having more than one distinct focus of DCIS with >5 mm of intervening benign breast tissue in one quadrant of the breast);
  7. High nuclear grade, including high nuclear grade in heterogeneous tumours;
  8. Associated microinvasive component;
  9. Presence of tumour cells in lymph nodes detected using H&E or immunohistochemical examination (if lymph node sentinel biopsy or dissection has been performed);
  10. Absolute contra-indication to whole-breast irradiation as determined by the referring physician;
  11. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03878342

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Contact: Naïma BONNET, PhD +33185343374

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Institut de Cancérologie de l'Ouest -Site Paul Papin Not yet recruiting
Angers, France
Contact: Aurore GOINEAU, MD         
Institut Sainte Catherine Not yet recruiting
Avignon, France
Contact: Antoine ARNAUD, MD         
Institut Bergonie Not yet recruiting
Bordeaux, France
Contact: Christel BRETON CALLU, MD         
Centre Jean Perrin Not yet recruiting
Clermont-Ferrand, France
Contact: Aurélie BELLIERE, MD         
Centre Georges Francois Leclerc Not yet recruiting
Dijon, France
Contact: Karine PEIGNAUX, MD         
Centre Oscar Lambret Not yet recruiting
Lille, France
Contact: David PASQUIER, MD         
Centre Hospitalier Bretagne Sud Not yet recruiting
Lorient, France
Contact: Guillaume BERA, MD         
Centre Léon Berard Not yet recruiting
Lyon, France
Contact: Violaine BENEYTON, MD         
Institut Regional Du Cancer Montpellier Val D Aurelle Not yet recruiting
Montpellier, France
Contact: Claire LEMANSKI, MD         
Institut CURIE Recruiting
Paris, France
Contact: Alain FOURQUET, MD         
Institut Jean Godinot Not yet recruiting
Reims, France
Contact: Nicolas MAGNE, MD         
Centre Henri Becquerel Not yet recruiting
Rouen, France
Contact: Chantal HANZEN, MD         
Institut De Cancerologie De Lorraine Alexis Vautrin Not yet recruiting
Vandœuvre-lès-Nancy, France
Contact: Myriam KHADIGE, MD         
Sponsors and Collaborators
National Cancer Institute, France
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Principal Investigator: Alain FOURQUET, MD Institut Curie
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Responsible Party: UNICANCER Identifier: NCT03878342    
Other Study ID Numbers: UC-0107/1803
First Posted: March 18, 2019    Key Record Dates
Last Update Posted: July 28, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type