Medial vs. Entire Supraclavicular Lymph Node Radiation Therapy for Patients With Invasive Breast Cancer (SUCLANODE)

A Multicenter Randomized Controlled Phase III Study of Medial vs. Entire Supraclavicualr Lymph Node Radiation Therapy for Patients With Pathologically Positive Axillary Lymph Node and High Risk of Recurrence After Breast Cancer Surgery

Locally advanced breast cancer has high-risk local regional recurrence after surgery. Radiotherapy could reduce the local regional recurrence and improve disease free survival and overall survival. Regional lymph node irradiation is the important part of breast cancer radiotherapy. However, there are some controversies about regional lymph node delineation, especially the supraclavicular irradiation volume. Many studies had confirmed that posterolateral region of the supraclavicular fossa (also named Posterior neck lymph node) had a high risk involvement based on the mapping of recurrence nodes. This randomized phase III trial compares medial supraclavicular lymph node irradiation with entire supraclavicular lymph node irradiation in patients with pathologically positive axillary lymph node and high risk of recurrence after mastectomy or breast conservative surgery. It is not yet known if radiation works better with entire supraclavicular fossa than medial supraclavicular fossa.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Radiotherapy; Complications; Effect of Radiation Therapy
• Intervention / Treatment: Radiation: Medial supraclavicular lymph node radiotherapy; Radiation: Entire supraclavicular lymph node radiotherapy

Detailed Description

PRIMARY OBJIECTIVE:

I. To evaluate whether entire supraclavicular lymph node irradiation is superior to medial supraclavicular lymph node irradiation in terms of disease free survival for patients with positive lymph nodes and high risk of recurrence after breast cancer surgery

SECONDARY OBJECTIVES:

I. To estimate the difference of overall survival II. to estimate the difference of ipsilateral supraclavicular node recurrence III. to estimate the difference of local regional recurrence IV. to estimate the difference of radiation related toxicities and quality of life.

Outline: Beginning 2-12 weeks after the completion of breast cancer surgery and neoadjuvant/adjuvant chemotherapy, patients are randomized to 1 of 2 treatment arms Arm I: Patients undergo breast/chest wall, undissected axillary, internal mammary node and medial supraclavicular node radiation. Conventional fractionated radiotherapy 50Gy/25Fx/5w or hypofractionated 42.5Gy/16Fx/3.5week with IMRT or VAMT technique is recommended. 3DCRT technique is not permitted.

Arm II: Patients undergo breast/chest wall, undissected axillary, internal mammary node and entire supraclavicular node radiation. Conventional fractionated radiotherapy 50Gy/25Fx/5w or hypofractionated 42.5Gy/16Fx/3.5week with IMRT or VAMT technique is recommended. 3DCRT technique is not permitted

• Study Type: Interventional
• Enrollment (Anticipated): 1650
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhaozhi Yang, M.D.; Phone Number: 86 18017317126; Email: yzzhi2014@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Zhaozhi C Yang; Phone Number: +8618017317126; Email: yzzhi2014@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. ECOG 0-1
2. Newly diagnosed invasive breast cancer
3. Initial clincial diagonosis stage is T1-4, N0-3a/b, M0: If neoadjuvant chemotherapy was not administered: pathological stage is T1-3N2-3a/b, M0; If neoadjuvant chemotherapy was administered：clinical stage III or pathological stage is T1-4N1-3a/bM0.
4. Underwent breast conservative surgery or Mastectomy with or without breast reconstruction with clear negative margin. At least, axillary level I and level II should be cleared with ≥10 lymph node (including the number of sentinal lymph node) . Level III dissection and internal mamamry node dissection are not required, but may be performed at the discretion of the surgeon.
5. Should receive ≥6 cycles standard neoadjuvant and/or adjuvant chemotherapy (taxane and/or anthracycline based).
6. Enrolled on the trial within 12 weeks of the later of two dates: the final breast cancer surgical procedure or administration of the last cycle of cytotoxic chemotherapy.
7. For ER and/or PR positive patients, the duration of anticipated endocrine therapy should be≥5 year ; For HER2 postive patients, the duration of anticipated herceptin should be 1 year.
8. Writtern, informed consent.

Exclusion Criteria:

1. Initinal clinical diagnosis N3c (supraclavicualr node metastasis)
2. T4 or inflamed breast cancer with no good downstage by neoadjuvant chemotherapy
3. Distant metastasis
4. Bilateral breast cancer or previously contralateral breast cancer
5. Positve sentinal lymph node with no axillary dissection
6. ECOG ≥2
7. Could not tolerate chemotherapy and anti-HER2 target treatment
8. Active infectious
9. History of radiotherapy
10. Serious medical complcation
11. Breast cancer during pregnancy and lactation
12. Had simultaneousl or previous secondary malignancies, except for skin basal cell carcinoma and cervical carcinoma in situ.

13. Inaccessibility for follow-up

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Breast/chest wall+undisseted axillary+IMN+medial SCL ( medial SCL radiation); Radiation is delivered to the breast/chest wall, undissected axilla, internal mammary nodes and medial supraclavicular node. Treatment will be given by normfractionated or hypofractionated radiotherapy (50Gy/25Fx/5w or 42.5Gy/16Fx/3.5w). IMRT and VMAT technique are recommended.	Radiation: Medial supraclavicular lymph node radiotherapy; Radiation is delivered to the breast/chest wall, undissected axilla, internal mammary nodes and entire supraclavicular lymph node.
Experimental: Breast/chest wall+undisseted axillary+IMN+entie SCL (entire SCL radiation); Radiation is delivered to the breast/chest wall, undissected axilla, internal mammary nodes and entire supraclavicular node. Treatment will be given by normfractionated or hypofractionated radiotherapy (50Gy/25Fx/5w or 42.5Gy/16Fx/3.5w). IMRT and VMAT technique are recommended.	Radiation: Entire supraclavicular lymph node radiotherapy; Radiation is delivered to the breast/chest wall, undissected axilla, internal mammary nodes and entire supraclavicular lymph node. Entire supraclavicular lymph node includes medial supraclavicular and posterior neck lymph node.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival (DFS )	defined as time from randomization until to local, regional, or distant recurrence, or any death, or secondary primary cancer	Up to 5 years after completion of radiation therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	defined as time from any death	Up to 5 years after completion of radiation therapy
Ipsilateral supraclavicular lymph node recurrence (ISLNR) )	defined as entire ipsilateral supraclavicular lymph node recurrence	Up to 5 years after completion of radiation therapy
Local reigonal recurrence (LRR)	chest wall, breast , regional lymph node recurrence	Up to 5 years after completion of radiation therapy
Distance metastasis (DS)	any recurrence in all areas beyond local, regional and death due to breast cancer	Up to 5 years after completion of radiation therapy
incidence of adverse events	Adverse events categorized using the NCI Common Terminology for Adverse Events Version 4.0 (CTCAE v4.0)	Up to 5 years after completion of radiation therapy
difference of quality of life	evaluate the quality of life according to EROTC-QLQ-C30 and QLQ BR23	Up to 5 years after completion of radiation therapy
differences in upper limb function	evaluate the upper limb function by Quick-dash	Up to 5 years after completion of radiation therapy

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Affiliated Hospital of Jiangnan University; Guizhou Provincial People's Hospital; The First Affiliated Hospital of University of Science and Technology of China; Quanzhou First Hospital; Jiangyin People's Hospital
• Investigators: Principal Investigator: Zhaozhi Yang, M.D, Fudan University; Study Chair: Xiaomao Guo, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Anticipated): August 1, 2026
• Study Completion (Anticipated): August 1, 2027

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 19, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 17, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; radiotherapy; supraclavicular lymph node
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: FDRT-BC017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No