Hypofractionated Vs Conventional Fractionated Postmastectomy Radiotherapy for High Risk Breast Cancer

Official title

Postmastectomy Hypofractionated Versus Conventional Fractionated Radiotherapy in High Risk Breast Cancer: a Phase III Randomized Clinical Trial

Overview

The study was designed to investigate whether hypofractionated adjuvant radiotherapy is noninferior to conventionally fractionated adjuvant radiotherapy in terms of efficacy and toxicities for high risk breast cancer patients treated with mastectomy

Detailed description

The randomization is between 50 Gy / 25 fractions and 42.5 Gy/16 fractions, 5 fractions weekly.

Eligible breast cancer patients with mastectomy and axillary dissection will be randomized 1:1 into two groups: conventional fractionated (CF) radiotherapy of 50 Gy / 25 fractions and hypofractionated (HF) radiotherapy of 42.5 Gy/16 fractions, 5 fractions weekly.

The primary endpoint is loco-regional recurrence. Other cancer related events and acute/late radiation morbidities will also be evaluated. The patients will be followed for 10 years.

It is hypothesized that for women operated for high risk breast cancer with indication of postmastectomy adjuvant radiotherapy, hypofractionated radiotherapy is noninferior to conventional fractionated radiotherapy in terms of the efficacy and toxicities.

Interventions

• Radiation Hypofractionated
  daily fractions, five fractions per week.
• Radiation Conventional
  daily fractions, five fractions per week.

Primary outcome measures

• Loco-regional recurrence (LRR) [Time frame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years]

Secondary outcome measures (12)

• Distant metastasis free survival (DMFS) [Time frame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years]
• Disease free survival (DFS) [Time frame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years]
• Overall survival (OS) [Time frame: every 3 months during the first 2 years after the last fraction received, every 6 months during 3-5 years, every year during 6-10 years]
• CTCAE Toxicity Assessment-Acute toxicity [Time frame: before treatment, every week of treatment, the end of treatment, 2 weeks, 3 months after the last fraction received, every year through 10 years]
• CTCAE Toxicity Assessment-Late toxicity [Time frame: before treatment, every year after the last fraction received through 10 years]
• LENT-SOMA Toxicity Assessment [Time frame: before treatment, every year after the last fraction received through 10 years]
• Number of patients with Arm Lymphedema [Time frame: before treatment, every year after the last fraction received through 10 years]
• Number of patients with impaired shoulder movement (Range of motion of the shoulders) [Time frame: before treatment, every year after the last fraction received through 10 years]
• Number of patients with symptomatic rib fracture [Time frame: before treatment, every year after the last fraction received through 10 years]
• Number of patients with brachial plexopathy [Time frame: before treatment, every year after the last fraction received through 10 years]
• Number of patients with reconstruction complications [Time frame: before treatment, every year after the last fraction received through 10 years]
• Cosmetic outcomes for patients received mastectomy with reconstruction [Time frame: before treatment, every year after the last fraction received through 10 years]

Eligibility criteria

Inclusion criteria

• Female
• Age18-75 years
• Pathologically confirmed invasive breast cancer
• Treated with mastectomy and axillary lymph node dissection with more than 10 resected lymph nodes. Immediate or delayed ipsilateral breast cancer reconstruction is accepted
• Negative surgical margins
• Pathologic T1-2N1 with at least one of the following risk factors: <40 years, Grade 3, lymphovascular invasion positive, ER/PR negative or HER2 overexpression, or pT3-4, or pN2-3 (four or more positive axillary lymph nodes)
• No distant metastases
• No supraclavicular or internal mammary nodes metastases
• ECOG:0-1
• Adjuvant systemic therapy with chemotherapy, endocrine therapy and anti-HER2 treatment is accepted.
• No neoadjuvant chemotherapy
• Fit for postoperative radiotherapy. No contraindications to radiotherapy
• Signed informed consent

Exclusion criteria

• Concurrent or previous malignancy excluding basal or squamous cell carcinoma of the skin
• Previous radiotherapy to the chest wall or regional lymph node areas
• Patients with severe non-malignant comorbidity in cardiovascular or respiration system
• Patients with medical contraindication for radiotherapy: systemic lupus erythematosus, cirrhosis
• pT1-2N1 with none of the following risk factors: <40 years, Grade 3, lymphovascular invasion positive, ER/PR negative or HER2 overexpression
• Patients with supraclavicular or internal mammary nodes metastases
• Known definitive clinical or radiologic evidence of metastatic disease
• Bilateral breast cancer or historically confirmed contralateral invasive breast cancer
• Treated with neoadjuvant chemotherapy
• ECOG: 3-4
• Pregnant or lactating
• Conditions indicating that the patient cannot go through the radiation therapy or follow up
• Unable or unwilling to sign informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Suzhou Municipal hospital — Suzhou
• Fudan University Shanghai Cancer Center — Shanghai
• Huangpu Branch, Shanghai ninth people's hospital — Shanghai

Identifiers

NCT: NCT03856372 · FDRT-BC008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗