Radiotherapy Versus Low-Dose Tamoxifen Following Breast Conserving Surgery for Low-Risk Breast Ductal Carcinoma in Situ

NCT04046159 | Unknown Phase 3 DMC

• 1 other identifier: 201902048MINC
• Study Type: interventional
• Target: 810
• Locations: 1 country
• Sites: 1

Brief Summary

Although the results obtained from ECOG E5194 cohort 1 (criteria: mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm) and RTOG 9804 trial (the same enrolled clinicopathological features to cohort 1 of ECOG E5194 trial) demonstrated that the 7-year ipsilateral breast tumor recurrence (IBTR) ranged from 5.6% to 10.5% for low-risk ductal carcinoma in situ (DCIS) patients, the aforementioned two studies included a proportional patients who had young age and negative estrogen receptor (ER) status tumor. Previous studies and our studies revealed that age \< 40 years and ER-negative status in tumor were independent prognostic factor for recurrence of breast DCIS irrespective of tumor characteristics. The UK/ANZ randomized trial, enrolling high-risk and low-risk clinicopathologic features of DCIS, demonstrated that a benefit of tamoxifen in terms of reducing the IBTR is observed in the BCS alone group but not found in the BCS plus RT group. A recent published randomized trial showed that tamoxifen at the dose of 5 mg/day for 3 years. Based on the aforementioned results, we hypothesized that the administration of tamoxifen is not inferior than the prescription of RT in terms of reducing the IBTR for DCIS patients who had age more than 40 years, the pathological features meeting the ECOG E5194 cohort 1 criteria, and positive ER status in tumors. To approve the hypothesis, we will design a randomized non-inferiority trial to assess whether the effect of administration of tamoxfien (5 mg per day) for 10 years following BCS is not inferior in terms of reducing IBTR when comparing RT following BCS for patients who had low-risk clinicopathologic features (age more than 40 years and ECOG E5194 cohort 1 criteria) and positive-ER status of breast DCIS.

Conditions

Breast Ductal Carcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• Breast tumor recurrence

  Ispilateral, regional recurrence, contralateral recurrence, and distant recurrence \[DCIS or invasive cancer event\]

  through study completion, an average of 1 year

Secondary Outcomes (2)

• The overall survival

  through study completion, an average of 1 year

• Adverse effects

  through study completion, an average of 1 year

Study Arms (2)

Radiotherapy arm

ACTIVE COMPARATOR

Radiotherapy for ipsilateral whole breast with 50 Gy/25 fractions or 40.05 Gy/15 fractions

Radiation: Whole breast radiotherapy

Tamoxifen arm

EXPERIMENTAL

Tamoxifen 5 mg QD for 10 years

Drug: Low-dose tamoxifen

Interventions

Low-dose tamoxifen DRUG

Low-dose tamoxifen is not inferior than radiotherapy in decreasing ipsilateral breast tumor recurrence and side effect

Also known as: LDT

Tamoxifen arm

Whole breast radiotherapy RADIATION

Ipsilateral breast tumor recurrence and side effect

Also known as: WBRT

Radiotherapy arm

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women
• New histologically diagnosed breast ductal carcinoma in situ (DCIS).
• Age ≥ 40 years
• Low risks of BRCA (breast cancer)1 and BRCA2: Manchester Score \< 10
• The DCIS must be detected by mammogram and must be unicentric, and no-mass lesion.
• Status post breast conserving surgery
• Pathological characteristics (all characteristics) 7.1 Lesions ≤ 2.5 cm in greatest dimension on pathologic specimen (use the largest measured size from the pathology report to obtain the required measurement of ≤ 2.5 cm).
• Must be classified as low or intermediate nuclear grade DCIS but without comedo necrosis according to Pathologic Guidelines (section 9.2.2) 7.3 Margins as assessed by the ink method will be 3 mm or greater. 7.4 Must be estrogen receptor (ER)-positive DCIS, ER percentage must be ≥10%
• Clinically node negative.

You may not qualify if:

• Known BRCA1 or BRCA2 mutation
• Age \< 40 years
• Women whose DCIS is palpable at the time of diagnosis, or multi-centric (mammography), or mass (mammography), or who have bloody nipple discharge.
• Pathological characteristics 4.1 Lesions measuring greater than 2.5 cm in greatest dimension on pathologic specimen.
• High-grade lesions or low to intermediate grade with comedo necrosis as classified by the Guidelines.
• Margins as assessed by the ink method will be less than 3 mm. 4.4. ER-negative DCIS or ER-positive percentage \< 10% in tumor cells
• Post-mastectomy patients
• Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer.
• Evidence of clinically significant cardiac disease, as defined by cardiac disease (New York Cardiac disease grade II), history of myocardial infarction, cerebral stroke, unstable arrhythmia, and unstable angina pectoris within 12 months before study entry.
• Pregnant or lactating status.

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Tri-Service General Hospital: collaborator
• Koo Foundation Sun Yat-Sen Cancer Center: collaborator
• Kaohsiung Medical University: collaborator
• Kyoto University: collaborator
• Mackay Memorial Hospital: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

Related Publications (1)

• Kuo SH, Tseng LM, Chen ST, Sagara Y, Chang YC, Yeh HT, Kuo YL, Hung CC, Lu TP, Lee YH, Toi M, Huang CS. Radiotherapy versus low-dose tamoxifen following breast-conserving surgery for low-risk and estrogen receptor-positive breast ductal carcinoma in situ: an international open-label randomized non-inferiority trial (TBCC-ARO DCIS Trial). BMC Cancer. 2023 Sep 14;23(1):865. doi: 10.1186/s12885-023-11291-6.

  PMID: 37710198 DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Chiun-Sheng Huang, MD, PhD, MPH

  Department of Surgery, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chiun-Sheng Huang, MD, PhD, MPH

CONTACT

+(886)-2-87339036; huangcs@ntu.edu.tw

Sung-Hsin Kuo, M.D.,Ph.D

CONTACT

+886-223123456; shkuo101@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Non-inferiority trial

Study Record Dates

• First Submitted: July 7, 2019
• First Posted: August 6, 2019
• Study Start: April 30, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 6, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 5 years after completion of study
• Access Criteria: Will be available after contacting with Principle investigators

Locations

TW (1)