Clinical trial NCT04069884: RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer
Official title: RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Radiation
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
First posted: 2019-08-28
Enrollment: 540
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to validate whether clinically low-risk, and RecurIndex high-risk N1 patients receiving regional lymph node radiotherapy can further improve clinical outcomes.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old, ≤ 70 years old.
* Eastern Cooperative Oncology Group (ECOG) ≤ 2.
* Postoperative pathology is clearly diagnosed as invasive breast cancer.
* Meet the clinical definition of low risk: ①Axillary lymph node micrometastasis (N1mic) or ②N1 patients who meet the following conditions at the same time, a）Age ≥ 40 years old, b）Vascular tumor thrombus (LVI) negative or allow few positive LVI (excluding extensive or massive LVI), c）Three subtypes are allowed (Lumina A, Lumina B/HER2 negative, Lumina B/HER2 positive) , namely ER positive (ER ≥ 1%), HER2 negative (HER2 expression negative or + by IHC, or 2+ but negative by FISH) or ER positive (ER ≥ 1%), HER2 positive (3+ by IHC, or 2+ but positive by FISH).
* Postoperative pathological diagnosis of axillary lymph node status is any of the following: a. Sentinel lymph node biopsy or axillary lymph node dissection for micrometastasis (N1mic), b. Sentinel lymph node biopsy for 1-2 lymph node macrometastasis (N1sln), c. Sentinel lymph node biopsy + axillary lymph node dissection or simple axillary lymph node dissection for 1-3 lymph node metastasis (N1).
* The primary tumor and breast undergo breast-conserving surgery or total resection ± breast reconstruction (autologous/prosthetic).
* There must be adequate systemic examination (such as chest X-ray, B-ultrasound, CT, etc.) within 3 months before randomization of radiotherapy to confirm that there is no distant metastasis.
* No contralateral breast cancer must be confirmed by molybdenum target and/or MRI within 12 months before randomization of radiotherapy.
* At least 4 courses of adjuvant chemotherapy with anthracycline or taxane should be completed after surgery.
* Radiotherapy must be performed sequentially after the completion of adjuvant chemotherapy, starting no later than 8 weeks after the end of chemotherapy.
* The patient must have sufficient primary fresh frozen specimens or post-paraffin tissue sections for RecurIndex testing.
* No previous history of malignant tumors, except for basal cell carcinoma of the skin.
* Signed an informed consent form.

Exclusion Criteria:

* Postoperative radiotherapy was confirmed as T3-4, N0, N2-3, M1 lesion staging before enrollment.
* Receive any new adjuvant therapy before surgery, including chemotherapy, endocrine therapy, targeted therapy or radiation therapy.
* Patients who underwent total mastectomy and only sentinel lymph node biopsy.
* Have a history of contralateral breast cancer.
* History of chest radiotherapy.
* combined with severe heart, lung, liver, kidney, hematopoietic, neurological diseases, and mental illness.
* History of autoimmune diseases such as scleroderma or active lupus erythematosus.
* pregnant and lactating patients.
* Unable or unwilling to sign an informed consent form.

Primary outcomes:
measure: Invasive disease-free survival (IDFS)
timeFrame: 5 years
Secondary outcomes:
measure: Any first recurrence (AFR)
timeFrame: 5 years
measure: Local-regional recurrence free survival (LRFS)
timeFrame: 5 years
measure: Distant metastasis free survival (DMFS)
timeFrame: 5 years
measure: Recurrence free survival (RFS)
timeFrame: 5 years
measure: Overall Survival (OS)
timeFrame: 5 years
measure: Disease free survival (DFS)
timeFrame: 5 years
measure: Beast cancer specific mortality (BCSM)
timeFrame: 5 years
measure: Patient life quality measurement
timeFrame: 5 years
measure: Patient life quality measurement
timeFrame: 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
References:
citation: Cheng SH, Horng CF, West M, Huang E, Pittman J, Tsou MH, Dressman H, Chen CM, Tsai SY, Jian JJ, Liu MC, Nevins JR, Huang AT. Genomic prediction of locoregional recurrence after mastectomy in breast cancer. J Clin Oncol. 2006 Oct 1;24(28):4594-602. doi: 10.1200/JCO.2005.02.5676.
citation: Cheng SH, Horng CF, Huang TT, Huang ES, Tsou MH, Shi LS, Yu BL, Chen CM, Huang AT. An Eighteen-Gene Classifier Predicts Locoregional Recurrence in Post-Mastectomy Breast Cancer Patients. EBioMedicine. 2016 Feb 16;5:74-81. doi: 10.1016/j.ebiom.2016.02.022. eCollection 2016 Mar.
citation: Cheng SH, Horng CF, Clarke JL, Tsou MH, Tsai SY, Chen CM, Jian JJ, Liu MC, West M, Huang AT, Prosnitz LR. Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients. Int J Radiat Oncol Biol Phys. 2006 Apr 1;64(5):1401-9. doi: 10.1016/j.ijrobp.2005.11.015. Epub 2006 Feb 10.
citation: Cheng SH, Tsai SY, Yu BL, Horng CF, Chen CM, Jian JJ, Chu NM, Tsou MH, Liu MC, Huang AT, Prosnitz LR. Validating a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer. Int J Radiat Oncol Biol Phys. 2013 Mar 15;85(4):953-8. doi: 10.1016/j.ijrobp.2012.08.042. Epub 2012 Nov 1.
citation: Cheng SH, Huang TT, Cheng YH, Tan TBK, Horng CF, Wang YA, Brian NS, Shih LS, Yu BL. Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer. PLoS One. 2017 Sep 8;12(9):e0184372. doi: 10.1371/journal.pone.0184372. eCollection 2017.
citation: Huang TT, Pennarun N, Cheng YH, Horng CF, Lei J, Hung-Chun Cheng S. Gene expression profiling in prognosis of distant recurrence in HR-positive and HER2-negative breast cancer patients. Oncotarget. 2018 May 1;9(33):23173-23182. doi: 10.18632/oncotarget.25258. eCollection 2018 May 1.
citation: Pittman J, Huang E, Dressman H, Horng CF, Cheng SH, Tsou MH, Chen CM, Bild A, Iversen ES, Huang AT, Nevins JR, West M. Integrated modeling of clinical and gene expression information for personalized prediction of disease outcomes. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8431-6. doi: 10.1073/pnas.0401736101. Epub 2004 May 19.
citation: Huang E, Cheng SH, Dressman H, Pittman J, Tsou MH, Horng CF, Bild A, Iversen ES, Liao M, Chen CM, West M, Nevins JR, Huang AT. Gene expression predictors of breast cancer outcomes. Lancet. 2003 May 10;361(9369):1590-6. doi: 10.1016/S0140-6736(03)13308-9.
citation: Huang TT, Chen AC, Lu TP, Lei L, Cheng SH. Clinical-Genomic Models of Node-Positive Breast Cancer: Training, Testing, and Validation. Int J Radiat Oncol Biol Phys. 2019 Nov 1;105(3):637-648. doi: 10.1016/j.ijrobp.2019.06.2546. Epub 2019 Jul 8.