Clinical trial NCT04517266: Evaluating Omitting of Internal Mammary Irradiation Among Early Stage Intermediate Risk (N1) Breast Cancer
Official title: Evaluating Omitting of Internal Mammary Irradiation Among Early Stage Intermediate Risk (N1) Breast Cancer Patients According to Clinical-genomic Model: an Open Label, Non-inferior Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
N1
clinical-genomic model
genomic model
radiotherapy
internal mammary irradiation
clinical model
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2020-08-18
Enrollment: 214
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The effect of internal mammary irradiation (IMI) added to whole-breast or thoracic-wall irradiation plus supraclavicular (SVC) irradiation after surgery on survival among women with early-stage intermediate risk (N1) breast cancer remains debated. The present study aimed to identified patient could be omitted from internal mammary lymph node irradiation by using a clinical-genomic model.

Detailed description: This study is a phase II open label, non-inferior randomized controlled trial, we aimed to compare the safety and effectiveness difference of whole breast/chest wall irradiation + IMI+SVC irradiation vs whole breast/chest wall irradiation + SVC irradiation among clinical high risk, genomic low risk of N1 breast cancer.

In previous studies, 28 gene classifier has been developed and established to predict local/regional recurrence. The 28 gene classifier was combined with 18 cancer gene and 10 reference gene. The 18 cancer gene includes BLM, TCF3, PIM1, RCHY1, PTI1,DDX39, BUB1B, STIL, TPX2, CCNB1,MMP15, CCR1,NFATC2IP, TRPV6,OBSL1, C16ORF7,DTX2, and ENSA. The expression of RCHY1, PTI1, ENSA, and TRPV6 is associated with better tumor biology and disease control. The remaining 14 genes are associated with poor outcomes. By using the 18-gene scoring algorithm defines the risk of recurrence as: low risk or high risk.

A total of five clinical factors \[age（≤40 vs. \>40, number of positive lymph node（1-2 vs. 3）, grade(I-II vs. III), tumor size (T1-T2), ki-67(\<14% vs. ≥14%)\] were identified to be significantly associated with outcomes of breast cancer in our previous study. And patients with more than 2 risk factors were defined as clinical high risk.

Clinical high risk participants (≥2 factors) with low-risk scores will be randomized to whole breast/chest wall irradiation + IMI+SVC irradiation or whole breast/chest wall irradiation + SVC irradiation

Eligibility criteria: Inclusion Criteria:

* • Histologically confirmed invasive breast cancer

  * Underwent radical surgery with either mastectomy or breast conserving surgery and axillary lymph node dissection (ALND)
  * The number of positive lymph node should be 1-3 (N1).
  * Clinical high risk breast cancer (≥2 clinical risk factors)
  * Aged 18-80 years old
  * ECOG performance status ≤2 (Karnofsky ≥70%) Anticipative overall survival \>5 years Pathologically surgical margin \>2mm ER (estrogen-receptor), PR (progesterone-receptor), HER2 (human epidermal growth factor receptor 2) and Ki67 testing can be performed on the primary breast tumor Women of child-bearing potential must agree to use adequate contraception for up to 1 month before study treatment and the duration of study participation Ability to understand and willingness to participate the research and sign the consent form

Exclusion Criteria:

* • Axillary dissection of less than 10 lymph nodes

  * Pathologically positive ipsilateral supraclavicular lymph node
  * Pathologically or radiologically confirmed involvement of ipsilateral internal mammary lymph nodes
  * Pregnant or lactating women
  * Treated with breast reconstruction surgery
  * Severe non-neoplastic medical comorbidities
  * History of non-breast malignancy within 5 years with the exception of lobular carcinoma in situ, basal cell carcinoma of the skin, carcinoma in situ of skin and carcinoma in situ of the cervix
  * simultaneous contralateral breast cancer
  * Previous radiotherapy to the neck, chest and/or ipsilateral axillary region
  * Active collagen vascular disease
  * Definitive pathological or radiologic evidence of distant metastatic disease
  * Primary T4 tumor
  * Interval between radical surgery (mastectomy or breast conserving surgery) and radiotherapy was more than 12 weeks or interval between last dose of adjuvant chemotherapy and radiotherapy was more than 8 weeks

Primary outcomes:
measure: 2-year event-free survival
timeFrame: 2 years
Secondary outcomes:
measure: 5-year event-free survival
timeFrame: 5 years
measure: 5-year overall survival
timeFrame: 5 years
measure: 5-year Locoregional recurrence (LRR)
timeFrame: 5-years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai jiaotong univestigy school of medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Wei-Xiang Qi, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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, 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: Qi WX, Cao L, Xu C, Zhao S, Chen J. Adjuvant regional nodal irradiation did not improve outcomes in T1-2N1 breast cancer after breast-conserving surgery: A propensity score matching analysis of BIG02/98 and BCIRG005 trials. Breast. 2020 Feb;49:165-170. doi: 10.1016/j.breast.2019.11.001. Epub 2019 Nov 29.