Clinical trial NCT02690636: Conventional Versus Hypofractionated Radiotherapy in Node Positive Breast Cancer
Official title: Conventional Versus Hypofractionated Adjuvant Radiotherapy in Node Positive Breast Cancer. Phase III, Open Label, Randomized Trial. Comparing Local Control, Cosmetic Outcome, Arm Lymph Edema and Health Economic Perspectives
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Mit Ghamr Oncology Center
name: Clinical Oncology department. Elmansoura University.
name: Zagazig University
name: Assiut University
name: Tanta University
name: Al-Azhar University
name: Medical Research Institute. Department of Cancer Management and Research.
name: Cairo University
name: Clinical Oncology Department. Banha University.
name: Ayadi El Mostakbal Cancer Center. Alexandria.
First posted: 2016-02-24
Enrollment: 500
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Breast cancer patients operated with modified radical mastectomy or breast conservative surgery will be randomized for either adjuvant conventional radiotherapy versus hypofractionated radiotherapy for chest wall and axilla or breast and axilla.

The patients will be recruited for one year and will be followed for 5 years by monitoring local recurrence, cosmetic outcomes, health economic perspectives, and arm lymph edema.

Detailed description: The investigators hypothesize that hypofractionated radiotherapy in node positive breast cancer is equally effective and safe as conventional fractionated radiotherapy. Breast cancer patients with pathological positive lymph nodes (N1 - N2) operated with modified radical mastectomy will be randomized 1:1 and also those with breast conservative surgery with positive lymph nodes will be randomized 1:1 for receiving either adjuvant conventional radiotherapy 200cgy x 25 fractions with 200cgy x 5 fractions boost for those with intact breast versus hypofractionated radiotherapy 266cgyx16 fractions and 266 cgy x 4 fractions boost for those with intact breast. The patients will be followed for 5 years to monitor locoregional recurrence, cosmetic outcomes, ipsilateral arm lymph edema. Health economic perspectives will be monitored by calculating cost effective analysis for both treatment plans.

Eligibility criteria: Inclusion Criteria:

1. ECOG. (Eastern Cooperative Oncology Group): 0-2
2. Histologic documentation of invasive duct or lobular adenocarcinoma of the breast
3. If neoadjuvant chemotherapy was NOT administered: pathologic T1-3, N1-2 following definitive surgery
4. If neoadjuvant chemotherapy was administered, pathology from the definitive surgery must confirm pathologic T1-3, N1-2 disease and also meet one of the following criteria:

   Clinical T1-3, N1-2 or Pathologic confirmation of axillary nodal involvement at presentation (ie, before neoadjuvant therapy) based on any of the following: Positive fine-needle aspiration (FNA), Positive core needle biopsy.
5. Complete resection of known breast disease by one of the following surgeries Lumpectomy with axillary lymph node dissection with no more than 12 resected lymph nodes.

Mastectomy and axillary lymph node dissection with no more than 12 resected lymph nodes.

5- ER(estrogen-receptor), PR (progesterone-receptor), and HER2(human epidermal growth factor receptor 2) testing performed on the primary breast tumor; when applicable, testing must have been performed before receiving neoadjuvant chemotherapy.

6-Margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the pathologist.

7-The surgical wound should be completely healed without any signs of infection.

8-Interval between the last surgery for breast cancer or the completion of adjuvant chemotherapy and study enrollment must be ≤ 56 days (ie, a maximum of 8 weeks).

9-If adjuvant chemotherapy is received there should be at least 10 days gap between the last day of chemotherapy and the enrollment in the study to avoid skin toxicity.

10-Women of child-bearing potential must agree to use a medically accepted form of pregnancy prevention for the duration of study treatment 11-Ability to understand and willingness to sign the consent form written in Arabic

Exclusion Criteria:

1. Patients with surgical margins less than or equal to 2mm.
2. Patients with axillary dissection of more than 12 lymph nodes due to high incidence of arm lymphedema.
3. Women with Huge pendulous breast.
4. Patients with bad breast conservative surgery ( Surgery that impair the cosmetic outcome before starting radiotherapy).
5. T4 tumors including inflammatory breast cancer.
6. Known definitive clinical or radiologic evidence of metastatic disease.
7. Patients re operated for microscopic positive margins after definitive surgery.
8. Previous radiation therapy for the currently diagnosed breast cancer prior to study enrollment
9. History of ipsilateral or contralateral breast or thoracic radiotherapy for any condition
10. History of ipsilateral or contralateral axillary surgery for any condition
11. History of lymphedema involving the ipsilateral or contralateral arm at present or at any time in the past
12. Active collagen vascular disease, specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus erythematosis, or scleroderma.
13. Pregnancy or breastfeeding
14. Second primary cancer.

Primary outcomes:
measure: Locoregional recurrence
timeFrame: 5 years
measure: Cosmetic outcomes
timeFrame: 5 years
measure: Arm lymph edema.
timeFrame: 5 years
measure: Health economic perspectives
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Mahmoud Ellithy
state: Abbasia
Study officials:
affiliation: Ain Shams University
name: Mahmoud Ellithy, Phd
role: PRINCIPAL_INVESTIGATOR
References: