Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Database of Safe Personalized Adjuvant Breast Radiotherapy Based on Individual Radiosensitivity (SAHARA-01)

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.
 
ClinicalTrials.gov Identifier: NCT04282122
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary:

Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as a poor cosmetic outcome following breast cancer can have a negative impact on quality of life and a marked effect on subsequent psychological outcome. Nevertheless, current practice standards commonly prescribe radiation dose and volume without regard to individual radiosensitivity.

In that context, a normal tissue radiosensitivity test that includes a rapid (72 h) radiosensitivity assay based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA) and other significant clinical parameters (multifactorial nomogram) was developed.

Omission of radiotherapy has been suggested when luminal A tumor subtype is combined with clinical and pathologic factors defining a subgroup of patients with a low risk of ipsilateral breast recurrence. In this group, the benefits of radiotherapy are small [6].

Reduction of the breast irradiated volume is also a possibility that has been tested and published using IORT, brachytherapy or external beam radiotherapy.

Hypofractionation has been adapted to breast cancer radiotherapy. Overall, all recent clinical trials [13, 14] showed only few late effects when hypofractionation was delivered to the whole breast (WB). These results reinforce the need of patients' selection using the NovaGray Breast® test.

Our hypothesis is therefore that the different techniques (volume reduction or hypofractionation) as well as radiotherapy omission will significantly reduce grade ≥2 bf+ in a personalized approach (driven by a predictive assay of late effects) compared to WB hypofractionation in a selected population at low risk of breast recurrence.

We would like to establish a prospective evaluation of daily practice including the individual radiosensitivity test to the decision of daily practice


Condition or disease Intervention/treatment
Breast Cancer Radiation: Radiotherapy

Detailed Description:

Severe but also moderate toxicities after curative-intent radiotherapy (RT), such as a poor cosmetic outcome following breast cancer can have a negative impact on quality of life and a marked effect on subsequent psychological outcome. Nevertheless, current practice standards commonly prescribe radiation dose and volume without regard to individual radiosensitivity.

In that context, a normal tissue radiosensitivity test that includes a rapid (72 h) radiosensitivity assay based on flow cytometric assessment of radiation-induced CD8 T-lymphocyte apoptosis (RILA) and other significant clinical parameters (multifactorial nomogram) was developed. The NovaGray Breast® test combines both a biological analysis (radio-induced lymphocyte apoptosis) and a predictive analysis, including external parameters related to the patient and her treatment. A negative predictive value (>90%) was found in case of high RILA taken alone and a sensitivity of 80% to detect the toxicity with an initial AUC of 0.61. In addition, including significant clinical parameters, the AUC was increased to 0.69. Moreover, a prognosis model with RILA alone to predict the probability to develop a toxicity and performance of the model was increased with the inclusion of significant clinical parameters (C-Harell 0.61 >> 0.69).

The NovaGray Breast® test is now validated after two prospective trials, one French (PHRC) and one European (Requite FP7). RILA and other factors have been confirmed to be independent factors that increase significantly the appearance of severe breast fibrosis. All these data have been merged into a nomogram allowing a predictive tool for daily clinical practice and then to customize radiotherapy techniques and indications.

In the meantime, several treatment modifications have been suggested to reduce late effects after breast radiotherapy:

Omission of radiotherapy has been suggested when luminal A tumor subtype is combined with clinical and pathologic factors defining a subgroup of patients with a low risk of ipsilateral breast recurrence. In this group, the benefits of radiotherapy are small [6]. In addition, low risk of recurrence was confirmed in randomized trials in a highly selected population. However, omitting radiotherapy and using intrinsic subtyping and clinical factors is a substantial change in care and could be driven by the risk of toxicity.

Reduction of the breast irradiated volume is also a possibility that has been tested and published using IORT, brachytherapy or external beam radiotherapy. The first two techniques are reserved for trained and expert centres but showed encouraging results with low toxicity rates and recurrences. The recent experience of external partial breast irradiation (EPBI) with twice daily fractions regimen showed an increase risk of late side-effects leading to use hypofractionated EPBI (hEPBI) once daily, 5 days a week. This regimen could only be used in case of selecting patients with NovaGray Breast®test without individual risk of late effects.

Hypofractionation has been adapted to breast cancer radiotherapy. Overall, all recent clinical trials showed only few late effects when hypofractionation was delivered to the whole breast (WB). Nevertheless, It has been shown in the TRANS-FAST trial a significant decrease of grade ≥2 bf+ for increasing values of RILA in the same extent than observed with conventional fractional schedules. These results reinforce the need of patients' selection using the NovaGray Breast® test.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Establishment of a Prospective Evaluation of Daily Practice Including the Individual Radiosensitivity Test to the Decision of Daily Practice
Actual Study Start Date : May 23, 2019
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine



Intervention Details:
  • Radiation: Radiotherapy
    curative-intent radiotherapy


Primary Outcome Measures :
  1. Acute and late breast fibrosis rate [ Time Frame: Until the study completion: 5 years ]
    Describe the acute and late breast fibrosis rate in daily practice according to the individual radiosensitivity, assessed by the NovaGray RILA Breast® test


Secondary Outcome Measures :
  1. Quality of life according to the EORTC QLQ-C30 [ Time Frame: Until the study completion: 5 years ]
    Evaluate the quality of life according to the EORTC QLQ-C30



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients treated with safe adjuvant therapy by personalized radiation based on individual radiosensitivity after resection of breast tumor
Criteria

Inclusion Criteria:

  1. Compliant women ≥ 65 years old.
  2. Conservative breast cancer surgery.
  3. T1-T2; N sentinel negative/N0.
  4. Luminal A tumors.
  5. Tumor negative margins.
  6. Indication of whole breast irradiation only.
  7. Extension evaluation of disease will be proven negative (M0).
  8. Must be geographically accessible for follow-up.
  9. Written and dated informed consent.
  10. Affiliated to the French social security system.

Exclusion Criteria:

  1. Patients with distant metastases.
  2. Indications of node irradiation.
  3. Synchronous bilateral breast cancer.
  4. Patients treated by radical mastectomy.
  5. Patients with neoadjuvant therapy.
  6. Patients with previous or concomitant other (not breast cancer) malignancy within the past 3 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least three years.
  7. Patients with other unstable or untreated non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.
  8. Patients treated with systemic investigational drugs within the past 30 days

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 ClinicalTrials.gov identifier (NCT number): NCT04282122


Contacts
Layout table for location contacts
Contact: Jean-Pierre BLEUSE, MD 0467613102 ext +33 DRCI-icm105@icm.unicancer.fr

Locations
Layout table for location information
France
Institut Régional du Cancer de Montpellier Recruiting
Montpellier, Occ, France, 34298
Contact: Jean-Pierre BLEUSE, MD    0467613102 ext +33    DRCI-icm105@icm.unicancer.fr   
Principal Investigator: Céline BOURGIER, MD         
Sub-Investigator: Claire LEMANSKI, MD         
Sub-Investigator: Carmen LLACER MOSCARDO, MD         
Sub-Investigator: Marie CHARISSOUX, MD         
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Investigators
Layout table for investigator information
Study Chair: Céline BOURGIER, MD Institut Régional du Cancer de Montpellier (ICM)
Publications:
Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez Miguelez C, Slampa P, Allgäuer M, Lössl K, Polat B, Kovács G, Fischedick AR, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Pötter R, Gall C, Malzer M, Uter W, Polgár C; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016 Jan 16;387(10015):229-38. doi: 10.1016/S0140-6736(15)00471-7. Epub 2015 Oct 19.

Layout table for additonal information
Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT04282122    
Other Study ID Numbers: PROICM 2018-09 BSA
First Posted: February 24, 2020    Key Record Dates
Last Update Posted: February 24, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut du Cancer de Montpellier - Val d'Aurelle:
breast cancer
oncology
database
radiotherapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases