Conventional Versus Hypofractionated Radiotherapy in Node Positive Breast Cancer

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Primary Purpose

Status

Unknown status

Phase

Phase 3

Locations

Egypt

Study Type

Interventional

Intervention

radiotherapy

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

ECOG. (Eastern Cooperative Oncology Group): 0-2
Histologic documentation of invasive duct or lobular adenocarcinoma of the breast
If neoadjuvant chemotherapy was NOT administered: pathologic T1-3, N1-2 following definitive surgery
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.
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:

Patients with surgical margins less than or equal to 2mm.
Patients with axillary dissection of more than 12 lymph nodes due to high incidence of arm lymphedema.
Women with Huge pendulous breast.
Patients with bad breast conservative surgery ( Surgery that impair the cosmetic outcome before starting radiotherapy).
T4 tumors including inflammatory breast cancer.
Known definitive clinical or radiologic evidence of metastatic disease.
Patients re operated for microscopic positive margins after definitive surgery.
Previous radiation therapy for the currently diagnosed breast cancer prior to study enrollment
History of ipsilateral or contralateral breast or thoracic radiotherapy for any condition
History of ipsilateral or contralateral axillary surgery for any condition
History of lymphedema involving the ipsilateral or contralateral arm at present or at any time in the past
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.
Pregnancy or breastfeeding
Second primary cancer.

Sites / Locations

Mahmoud EllithyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Conventional

Hypofractionated

Arm Description

The patients will receive adjuvant radiotherapy conventionally fractionated 5000 cgy fractionated by 200cgy daily fractions, five fractions per week over 5 weeks with an additional 200cgy daily for five days as boost for patients with breast conservative surgery.

The patients will receive adjuvant radiotherapy hypofractionated 266cgy daily fractions, five fractions per week for total 16 fractions and an additional five daily fractions will be added as boost for patients with breast conservative surgery.

Outcomes

Primary Outcome Measures

Locoregional recurrence

Tumor locoregional recurrence is defined as: Any newly suspicious skin change/s or palpable lymph node in the irradiated area (compared to baseline photo and clinical examination of this area) that is/are pathologically proved to be locoregional tumor recurrence. Suspicious skin change/s and palpable lymph node from baseline photo and baseline clinical examination of the irradiated area will be monitored at 3 months throughout 5 years following the completion of radiotherapy in the two study arms to detect the incidence and time of locoregional recurrence.

Cosmetic outcomes

Aesthetic evaluation of the irradiated breast will be through 3 methods. Patient questionnaire (Subjective evaluation), Harvard score for breast cosmoses (Observer evaluation) and a computer soft ware that calculate the configuration difference between treated and non treated breast. Upon evaluation, each of the three methods will acquire a point ranging from 0 to 3 (poor to excellent cosmetic outcome respectively). The points of the three methods will be added yielding a score ranging from 0 to 9. Score 0-2, 3-4, 5-6 and 7-9 mean poor, fair, good and excellent cosmoses respectively. The cumulative incidence of changes in breast cosmoses from baseline for every patient will be assessed every year (as described above) through out the 5 years (Time frame of the study) following the completion of radiotherapy in the two study arms. By the end of the five years the aesthetic evaluation for each patient will be through calculating the average of her 5 years score.

Arm lymph edema.

To evaluate the cumulative incidence of lymph edema during the 5 years following completion of hypofractionated radiation treatment [ Time Frame: 5 years ] Incidence of lymphedema defined as ≥ 10% increase in arm circumference over baseline circumference compared to the contralateral arm measured every 6 months from the time of initiation of hypofractionated irradiation of breast and regional nodes through 5 years following the completion of radiation therapy in 2 study groups.

Health economic perspectives

The economic perspectives for the public health: (Time frame 5 years). Cost effective analysis of each treatment plan will be evaluated at the end of 5 years through calculation of the cost-effectiveness ratio = Cost of intervention / Health effect produced. The cost of intervention = the sum of (Cost of medical staff time, drugs and equipment maintenance during the 5 years time frame). (The cost of intervention during the 5 years time frame will be used for calculations). The health effect produced will be years of local control (Number of years the patient lived without any pathological evidence of local recurrence). (The mean years of local control during the 5 years time frame will be used for calculations). The treatment program with the less cost effectiveness ratio will be recommended for treating patients.

Secondary Outcome Measures

Full Information

NCT ID

NCT02690636

First Posted

January 29, 2016

Last Updated

May 29, 2016

Sponsor

Ain Shams University

Collaborators

Mit Ghamr Oncology Center, Clinical Oncology department. Elmansoura University., Zagazig University, Assiut University, Clinical Oncology department. Tanta University., Al-Azhar University, Medical Research Institute. Department of Cancer Management and Research., Cairo University, Clinical Oncology Department. Banha University., Ayadi El Mostakbal Cancer Center. Alexandria.

1. Study Identification

Unique Protocol Identification Number

NCT02690636

Brief Title

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

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Unknown status

Study Start Date

January 2016 (undefined)

Primary Completion Date

February 2021 (Anticipated)

Study Completion Date

April 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ain Shams University

Collaborators

Mit Ghamr Oncology Center, Clinical Oncology department. Elmansoura University., Zagazig University, Assiut University, Clinical Oncology department. Tanta University., Al-Azhar University, Medical Research Institute. Department of Cancer Management and Research., Cairo University, Clinical Oncology Department. Banha University., Ayadi El Mostakbal Cancer Center. Alexandria.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Conventional

Arm Type

Active Comparator

Arm Description

The patients will receive adjuvant radiotherapy conventionally fractionated 5000 cgy fractionated by 200cgy daily fractions, five fractions per week over 5 weeks with an additional 200cgy daily for five days as boost for patients with breast conservative surgery.

Arm Title

Hypofractionated

Arm Type

Experimental

Arm Description

The patients will receive adjuvant radiotherapy hypofractionated 266cgy daily fractions, five fractions per week for total 16 fractions and an additional five daily fractions will be added as boost for patients with breast conservative surgery.

Intervention Type

Radiation

Intervention Name(s)

radiotherapy

Intervention Description

daily fractions, five fractions per week.

Primary Outcome Measure Information:

Title

Locoregional recurrence

Description

Tumor locoregional recurrence is defined as: Any newly suspicious skin change/s or palpable lymph node in the irradiated area (compared to baseline photo and clinical examination of this area) that is/are pathologically proved to be locoregional tumor recurrence. Suspicious skin change/s and palpable lymph node from baseline photo and baseline clinical examination of the irradiated area will be monitored at 3 months throughout 5 years following the completion of radiotherapy in the two study arms to detect the incidence and time of locoregional recurrence.

Time Frame

5 years

Title

Cosmetic outcomes

Description

Aesthetic evaluation of the irradiated breast will be through 3 methods. Patient questionnaire (Subjective evaluation), Harvard score for breast cosmoses (Observer evaluation) and a computer soft ware that calculate the configuration difference between treated and non treated breast. Upon evaluation, each of the three methods will acquire a point ranging from 0 to 3 (poor to excellent cosmetic outcome respectively). The points of the three methods will be added yielding a score ranging from 0 to 9. Score 0-2, 3-4, 5-6 and 7-9 mean poor, fair, good and excellent cosmoses respectively. The cumulative incidence of changes in breast cosmoses from baseline for every patient will be assessed every year (as described above) through out the 5 years (Time frame of the study) following the completion of radiotherapy in the two study arms. By the end of the five years the aesthetic evaluation for each patient will be through calculating the average of her 5 years score.

Time Frame

5 years

Title

Arm lymph edema.

Description

To evaluate the cumulative incidence of lymph edema during the 5 years following completion of hypofractionated radiation treatment [ Time Frame: 5 years ] Incidence of lymphedema defined as ≥ 10% increase in arm circumference over baseline circumference compared to the contralateral arm measured every 6 months from the time of initiation of hypofractionated irradiation of breast and regional nodes through 5 years following the completion of radiation therapy in 2 study groups.

Time Frame

5 years

Title

Health economic perspectives

Description

The economic perspectives for the public health: (Time frame 5 years). Cost effective analysis of each treatment plan will be evaluated at the end of 5 years through calculation of the cost-effectiveness ratio = Cost of intervention / Health effect produced. The cost of intervention = the sum of (Cost of medical staff time, drugs and equipment maintenance during the 5 years time frame). (The cost of intervention during the 5 years time frame will be used for calculations). The health effect produced will be years of local control (Number of years the patient lived without any pathological evidence of local recurrence). (The mean years of local control during the 5 years time frame will be used for calculations). The treatment program with the less cost effectiveness ratio will be recommended for treating patients.

Time Frame

5 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: ECOG. (Eastern Cooperative Oncology Group): 0-2 Histologic documentation of invasive duct or lobular adenocarcinoma of the breast If neoadjuvant chemotherapy was NOT administered: pathologic T1-3, N1-2 following definitive surgery 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. 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: Patients with surgical margins less than or equal to 2mm. Patients with axillary dissection of more than 12 lymph nodes due to high incidence of arm lymphedema. Women with Huge pendulous breast. Patients with bad breast conservative surgery ( Surgery that impair the cosmetic outcome before starting radiotherapy). T4 tumors including inflammatory breast cancer. Known definitive clinical or radiologic evidence of metastatic disease. Patients re operated for microscopic positive margins after definitive surgery. Previous radiation therapy for the currently diagnosed breast cancer prior to study enrollment History of ipsilateral or contralateral breast or thoracic radiotherapy for any condition History of ipsilateral or contralateral axillary surgery for any condition History of lymphedema involving the ipsilateral or contralateral arm at present or at any time in the past 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. Pregnancy or breastfeeding Second primary cancer.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mahmoud Ellithy, Phd

Phone

01000069694

Ext

002

Email

ellithym@med.asu.edu.eg

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mahmoud Ellithy, Phd

Organizational Affiliation

Ain Shams University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mahmoud Ellithy

City

Cairo

State/Province

Abbasia

ZIP/Postal Code

14031

Country

Egypt

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mahmoud Ellithy, Phd

Phone

01000069694

Ext

002

Email

ellithym@med.asu.edu.eg

First Name & Middle Initial & Last Name & Degree

Heba Abdallah, Specialist

First Name & Middle Initial & Last Name & Degree

Ahmed Nagy, Consultant

First Name & Middle Initial & Last Name & Degree

Lamia Elwakil, Pharmacist

First Name & Middle Initial & Last Name & Degree

Noha Elboghdady, Pharmacist

First Name & Middle Initial & Last Name & Degree

Ahmad Abdel-Hady, Consultant

First Name & Middle Initial & Last Name & Degree

Wael Elsheshtawy, Consultant

First Name & Middle Initial & Last Name & Degree

Rasha Haggag, Consultat

First Name & Middle Initial & Last Name & Degree

Mohamed A. Alm El-Din, Consultant

First Name & Middle Initial & Last Name & Degree

Mostafa Elnaggar, Consultant

First Name & Middle Initial & Last Name & Degree

Marwa I. Abdelgawad, Consultant

First Name & Middle Initial & Last Name & Degree

Abdelmoneim Elsayed, Consultant

12. IPD Sharing Statement

Plan to Share IPD

No

Breast Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial