Radiation Therapy in Women With Low Risk Early-Stage Breast Cancer Who Have Undergone Breast Conservation Surgery (IMPORT)

Randomised Trial Testing Intensity Modulated and Partial Organ Radiotherapy After Breast Conservation Surgery for Early Breast Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether intensity-modulated radiation therapy is more effective than standard radiation therapy in treating patients with early-stage breast cancer.

PURPOSE: This randomized phase III trial is comparing radiation therapy regimens in treating women with early-stage breast cancer who have undergone breast-conservation surgery.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: radiation therapy

Detailed Description

OBJECTIVES:

• To test partial breast radiotherapy using intensity-modulated techniques following complete local tumor excision in women with low-risk, early stage breast cancer.

OUTLINE: This is a multicenter study.

Patients are stratified according to center (not participating in sub-studies vs participating in sub-studies). Patients are randomized to 1 of 3 treatment arms.

• Arm I (control): Patients undergo standard whole breast radiotherapy once daily on days 1-5 (15 fractions) for 3 weeks.
• Arm II: Patients undergo reduced whole breast radiotherapy (15 fractions) and standard partial breast radiotherapy (15 fractions) once daily on days 1-5 for 3 weeks.
• Arm III: Patients undergo standard partial breast radiotherapy once daily on days 1-5 (15 fractions) for 3 weeks.

All patients complete a family history questionnaire at baseline. Patients also undergo blood sample collection at baseline and paraffin-embedded tissue collection at follow-up for molecular studies analyzing inter-patient variation by microarrays.

Patients in centers participating in sub-studies undergo quality of life and health economic assessment at baseline, 6 months, and 1, 2, and 5 years. These patients also undergo photographic assessment at baseline, 2 years, and 5 years.

After completion of study treatment, patients are followed for 10 years.

• Study Type: Interventional
• Enrollment (Actual): 2018
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden - Surrey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Diagnosis of low-risk early stage breast cancer, meeting the following criteria:

  • Invasive adenocarcinoma

    • No invasive carcinoma of classical lobular type
    • lympho-vascular invasion present or absent
  • Tumor size pathologically determined to be ≤ 3.0 cm in diameter (pT1-2) (< 3.1 cm maximum microscopic diameter of invasive component)
  • Unifocal disease
  • Grade I, II, or III disease
  • Axillary lymph nodes negative or 1-3 nodes positive (pN0 or pN+(1-3))

• Must have undergone breast conservation surgery with or without adjuvant systemic therapy

  • Minimum microscopic margin of non-cancerous tissue ≥ 2 mm (excluding deep margin if this is at deep fascia)
• At low risk of local recurrence after radiotherapy (< 1% annual risk local recurrence)
• No prior mastectomy
• No blood-borne metastases

PATIENT CHARACTERISTICS:

• No prior malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior endocrine therapy or chemotherapy

  • Neoadjuvant endocrine therapy allowed provided the tumour is < 3.0 cm and all other inclusion criteria are met
  • No primary endocrine therapy as a replacement for surgery
• No concurrent chemoradiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (control); Patients undergo standard whole breast radiotherapy once daily on days 1-5 for 3 weeks.	Radiation: radiation therapy; Patients undergo standard whole breast, reduced whole breast, or standard partial breast radiotherapy
Experimental: Arm II; Patients undergo reduced whole breast radiotherapy and standard partial breast radiotherapy once daily on days 1-5 for 3 weeks.	Radiation: radiation therapy; Patients undergo standard whole breast, reduced whole breast, or standard partial breast radiotherapy
Experimental: Arm III; Patients undergo standard partial breast radiotherapy once daily on days 1-5 for 3 weeks.	Radiation: radiation therapy; Patients undergo standard whole breast, reduced whole breast, or standard partial breast radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local tumor control in the ipsilateral breast (i.e., true recurrence plus new primary tumor) as confirmed by cytological or histological assessment	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Location of tumor relapse	5 years
Contralateral primary breast cancer or other primary tumors as confirmed by cytological or histological assessment	5 years
Regional and distant metastases	5 years
Late adverse effects in normal tissue normal tissues as determined periodically by photographic assessments (in a subset of patients), physician assessments, and patient self-assessments	5 years
Quality of life as assessed by EORTC QLQ C-30, EORTC QLQ-BR23, BIS, and HADS questionnaires in a subset of patients at baseline, 6 months, and 1, 2, and 5 years	5 years
Cost-effectiveness as assessed by EQ-5D questionnaire at baseline, 6 months, and 1, 2, and 5 years	10 years

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Cancer Research UK
• Investigators: Principal Investigator: Charlotte E Coles, PhD, University of Cambrige, England

Publications and helpful links

General Publications

• Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, Bhattacharya IS, Brunt AM, Ciurlionis L, Chan C, Donovan EM, Emson MA, Harnett AN, Haviland JS, Hopwood P, Jefford ML, Kaggwa R, Sawyer EJ, Syndikus I, Tsang YM, Wheatley DA, Wilcox M, Yarnold JR, Bliss JM; IMPORT Trialists. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017 Sep 9;390(10099):1048-1060. doi: 10.1016/S0140-6736(17)31145-5. Epub 2017 Aug 2.
• Bhattacharya IS, Haviland JS, Kirby AM, Kirwan CC, Hopwood P, Yarnold JR, Bliss JM, Coles CE; IMPORT Trialists. Patient-Reported Outcomes Over 5 Years After Whole- or Partial-Breast Radiotherapy: Longitudinal Analysis of the IMPORT LOW (CRUK/06/003) Phase III Randomized Controlled Trial. J Clin Oncol. 2019 Feb 1;37(4):305-317. doi: 10.1200/JCO.18.00982. Epub 2018 Dec 11.
• Kirby AM, Bhattacharya IS, Wilcox M, Haviland JS. The IMPORT LOW Trial: Collaborative Research Accelerates Practice Change in Breast Radiotherapy. Clin Oncol (R Coll Radiol). 2019 Jan;31(1):5-8. doi: 10.1016/j.clon.2018.08.007. Epub 2018 Sep 17. No abstract available.
• Coles C, Yarnold J; IMPORT Trials Management Group. The IMPORT trials are launched (September 2006). Clin Oncol (R Coll Radiol). 2006 Oct;18(8):587-90. doi: 10.1016/j.clon.2006.07.010. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2007
• Primary Completion (Actual): June 15, 2016
• Study Completion (Anticipated): September 1, 2020

Study Registration Dates

• First Submitted: December 24, 2008
• First Submitted That Met QC Criteria: December 24, 2008
• First Posted (Estimate): December 25, 2008

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: recurrent breast cancer; stage II breast cancer; stage IA breast cancer; invasive ductal breast carcinoma; invasive ductal breast carcinoma with predominant intraductal component
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: CDR0000629768; NIHR 2253 (Other Identifier: NIHR); ICR-CTSU/2006/10001 (Other Identifier: ICR-CTSU); ISRCTN12852634 (Registry Identifier: ISRCTN); CRUK/06/003 (Other Grant/Funding Number: Cancer Research UK); 06/Q1605/128 (Other Identifier: Main Research Ethics Committee)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No