Resource-sparing Post-mastectomy Radiotherapy in Breast Cancer

Phase 3

• Conditions: Breast Cancer
• Interventions: Radiation: Irradiation of the chest-wall and supraclavicular fossa; Radiation: Radiotherapy

• Registration Number: NCT01452672
• Lead Sponsor: International Atomic Energy Agency

Brief Summary

This study compares two different field set-ups in patients with breast cancer following a breast resection (mastectomy). These two set-ups are as follows: arm a - radiotherapy to the chest-wall only, and arm b - radiotherapy to the chest-wall and the supraclavicular fossa.

Patients in both treatment arms will receive radiotherapy with a shortened fractionation schedule.

Study hypothesis: irradiation of the chest-wall only is not inferior to irradiation of the chest-wall and supraclavicular fossa in terms of loco-regional control, survival and treatment toxicity.

Detailed Description

Post-mastectomy radiotherapy (PMRT) substantially reduces the risk of loco- regional failure as shown in several studies and meta-analyses. Two large trials for pre-menopausal node-positive breast cancer patients treated with mastectomy and chemotherapy showed that PMRT not only reduced loco- regional failure rates but also improved disease-free and overall survival rates.

Although the benefit of PMRT is clear, the optimal volume of tissues to be covered by the radiotherapy fields is controversial. Since the chest wall is the most likely location of recurrence, there is uniform consensus that the chest wall should be irradiated. However, areas of controversy exist regarding irradiation of the regional lymph nodes (axillary, supraclavicular and internal mammary lymph nodes), optimal radiation dose, and dose-fractionation.

If equivalent results could be achieved by omitting irradiation of the supraclavicular region in patients receiving adjuvant systemic therapy, this will simplify and expedite treatment in this patient population. Furthermore, the use of a shortened fractionation schedule of 40 Gy in 15 fractions (2.67 Gy per fraction) over 3 weeks which has been used in the UK and Canada for post-mastectomy patients for several decades will shorten the duration of treatment by reducing the number of patient visits for radiotherapy and increase the number of patients who can be treated. Treatment will be more convenient for patients and a reduction in the number of treatments could result in savings for strained health care systems.

This is a randomized comparison of two different radiotherapy field set-ups for post-mastectomy treatment of locally advanced breast cancer. Patients who have undergone modified radical mastectomy including axillary lymph node dissection will be randomized to receive one of two radiotherapy treatment arms, A and B following the completion of adjuvant chemotherapy. The radiotherapy for treatment Arm A consists of irradiation of the chest wall only while Treatment Arm B includes irradiation of the chest wall and the ipsilateral supraclavicular field. Patients on both treatment arms will receive radiation with a shortened fractionation schedule. Patients will be evaluated for local control, regional control, survival and treatment toxicity.

Study Timeline

• Study Start: 2007-03
• Status Verified: 2011-10
• Study First Submitted: 2011-10-10
• Study First Submitted QC: 2011-10-14
• Last Update Submitted: 2011-10-14
• Study First Posted: 2011-10-17
• Last Update Posted: 2011-10-17
• Primary Completion: 2012-12
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 600

Inclusion Criteria

1. Patients must be older than 18 and less than 81 years of age

2. WHO (ECOG) Performance Status of 0-2

3. Histologically confirmed diagnosis of infiltrating ductal carcinoma of the breast, lobular carcinoma or mixed (ductal and lobular) type.

   Note: Tumor diagnosis will be performed at the participating center according to the center's routine procedures.

4. Patients must have had a modified radical mastectomy (MRM) in which 6 or more axillary nodes were removed.

5. All patients should receive adjuvant chemotherapy following MRM. The initiation of radiation therapy must allow for the full recovery of blood counts (WBC > 3.0 x 109/L, Granulocytes > 1.5 x109/L and platelets > 75 x 109/L).

   Note: MRM should have been performed at maximum 3 months prior to the start of adjuvant chemotherapy.

   Special Note: Patients who have not received adjuvant chemotherapy will be required to receive adjuvant chemotherapy as per Appendix 3 prior to study entry and initiation of radiotherapy must allow for the full recovery of blood counts (WBC > 3.0 x 109/L, Granulocytes > 1.5 x109/L and platelets > 75 x 109/L MRM should have been performed within 3 months prior to the start of adjuvant chemotherapy.

6. Patients must have received adjuvant chemotherapy according to one of the two regimens found in Appendix 3.

7. Negative surgical margins by histopathology at the time of MRM. Note: Negative surgical margins means that there are no cancer cells at the inked margin of resection or otherwise at the margins of the mastectomy specimen.

8. The following indicators in the histological samples must be known :

   1. Tumor size
   2. Tumor site (quadrant, central, axillary tail)
   3. Presence of extensive intraductal component (EIC)
   4. Estrogen and Progesterone Receptor Status and the method of staining and detection.
   5. HER2 Status (optional), if given, the method must be provided.

9. Patients with the following TNM stages, all being M0: pT1 N1, pT2 N1, pT3 N0, pT0 N2, pT1 N2, pT2 N2, T3 N1, pT3 N2 (see Appendix 4 for TNM Stage)

10. Histological grades 1 - 3 (as per WHO criteria)

11. Patients must consent to return for scheduled treatments and follow up.

12. Written informed consent document signed

Exclusion Criteria

1. Pathological pN3 (metastasis in 10 or more lymph nodes, clinically apparent internal mammary metastasis, metastasis in the supraclavicular lymph nodes)
2. Stages IIIB, IIIC and IV (any T4, any N3 or M1)
3. Recurrence of breast cancer following MRM and/or adjuvant chemotherapy.
4. Concomitant primary cancer in the contralateral breast.
5. History of other malignancy except carcinoma in situ of the cervix or non-melanoma skin cancer
6. Pregnant or breast-feeding
7. Previous chemotherapy other than adjuvant chemotherapy for treatment of the present breast cancer
8. Other severe concomitant disease that could impact upon the ability to deliver treatment or increase the risk of toxicity (such as uncompensated congestive heart failure, unstable coronary heart disease, uncompensated chronic obstructive pulmonary disease, collagen vascular diseases including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and ataxia telangiectasia).
9. Contraindications to radiation therapy (such as previous irradiation of the breast or chest wall)
10. Severe psychiatric disorder that may interfere with the process of informed consent and/or treatment or follow-up compliance.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RT to chest wall and S/C	Irradiation of the chest-wall and supraclavicular fossa	Irradiation of the chest-wall and supraclavicular fossa
RT to chest wall	Radiotherapy	Irradiation of the chest-wall alone

Primary Outcome Measures

Name	Time	Method
Local control.	4 years	The presence/absence of recurrent disease in the surgical scar, ipsilateral chest wall, ipsilateral skin and soft tissue.
Regional control.	4 years	The presence/absence of recurrent disease in the axilla, ipsilateral supraclavicular/infraclavicular nodes and or ipsilateral skin/soft tissue in the regional areas.
Overall survival.	4 years
Disease-free survival.	4 years
Acute adverse events.	4 years	During treatment and up to 90 days following the completion of treatment.
Late adverse events.	4 years	More than 90 days after the completion of radiation therapy.

Secondary Outcome Measures

Name	Time	Method
Reproductive history.	1 year	Number of pregnancies, miscarriages. Menstrual History.
Characterization of molecular profile of breast cancer patients.	4 years
Family history.	1 year	Family history of breast cancer.
Patients' demographics.	4 years

Trial Locations

Locations (9)

Instituto Naciolal de Oncologia y Radiobiologia (INOR); 🇨🇺 Havana, Cuba

University of Ibadan College Hospital; 🇳🇬 Ibadan, Nigeria

Institut of Radiotherapy and Nuclear Medicine (IRNUM); 🇵🇰 Peshawar, Pakistan

Cerraphasa Medical Faculty; 🇹🇷 Istanbul, Turkey

Institut National d'Oncologie; 🇲🇦 Rabat, Morocco

Alexandria Ayadi Almostakbal Oncology Cenre.; 🇪🇬 Alexandria, Egypt

Korle Bu Teaching Hospital; 🇬🇭 Accra, Ghana

Cairo National Cancer Institute; 🇪🇬 Cairo, Fom El-Khalig, Egypt

Instituto Nacional de Enfermedades Neoplasicas; 🇵🇪 Lima, Peru