STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing) (STARS)

A Randomised Comparison of Anastrozole Commenced Before and Continued During Adjuvant Radiotherapy for Breast Cancer Versus Anastrozole and Subsequent Anti-oestrogen Therapy Delayed Until After Radiotherapy.

The purpose of this study is to determine whether starting anastrozole prior to radiotherapy, so that it is taken during radiotherapy, decreases local recurrence of breast cancer in post-menopausal women in comparison to waiting until after radiotherapy to commence anastrozole.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pre-radiotherapy commencement of anastrozole; Radiation: Radiotherapy; Drug: Post radiotherapy commencement of anastrozole

Detailed Description

Adjuvant radiotherapy is well established as the primary modality to enhance local control in breast cancer. The use of adjuvant hormone therapy such as tamoxifen has shown to improve local control to a relatively minor amount on its own and does enhance local control of adjuvant radiotherapy. There is, however, conflicting invitro and clinical data regarding the effects or different sequences on tamoxifen and radiotherapy in terms of both local control and enhancement of radiotherapy toxicities.

Aromatase inhibitors such as anastrozole are establishing themselves as a class of drug superior to tamoxifen for the control of estrogen dependent breast cancers and overall are better tolerated with the exception of greater bone loss.

As the key question is whether the sequencing of the aromatase inhibitor anastrozole alters local control by acting as an enhancer of the radiation breast cancer cell kill, it is therefore the aim of this study to compare 3 months of anastrozole prior to radiotherapy versus 3 months of anastrozole after radiotherapy with a specific objective of reducing the baseline ratio of in-field radiotherapy failure from 6% to 3%.

• Study Type: Interventional
• Enrollment (Actual): 2023
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2605
      • The Canberra Hospital
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2560
      • Campbelltown Hospital
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Hurstville, New South Wales, Australia, 2220
      • Genesis Cancer Care Hurstville
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Newcastle, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
    • Orange, New South Wales, Australia
      • Central West Cancer Service
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Wagga Wagga, New South Wales, Australia, 2650
      • Riverina Cancer Centre
    • Wollongong, New South Wales, Australia, 2500
      • Illawarra Cancer Care Centre
  • Northern Territory
    • Darwin, Northern Territory, Australia, 811
      • Alan Walker Cancer Centre
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Genesis Cancer Care
    • Cairns, Queensland, Australia, 4350
      • Cairns ROQ
    • Chermside, Queensland, Australia, 4032
      • Genesis Cancer Care
    • Douglas, Queensland, Australia, 4810
      • The Townsville Hospital
    • Gold Coast, Queensland, Australia, 4217
      • Radiation Oncology Gold Coast
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Radiation Oncology - Mater Centre
    • Southport, Queensland, Australia
      • Genesis Southport
    • Toowoomba, Queensland, Australia, 4350
      • St Andrew's Toowoomba Hospital
    • Tugun, Queensland, Australia, 4224
      • Genesis Care
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Geelong Hospital
  • Western Australia
    • Bunbury, Western Australia, Australia
      • Genesis Cancer Care
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Perth, Western Australia, Australia, 6001
      • Royal Perth Hospital
    • Wembley, Western Australia, Australia, 6014
      • Perth Radiation Oncology
• New Zealand
  • Auckland, New Zealand
    • Auckland Hospital
  • Christchurch, New Zealand
    • Christchurch Hopsital Oncology Sevice
  • Palmerston North, New Zealand
    • Palmerston North

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women aged 18 years or older
• Post total mastectomy or lumpectomy. All planned cancer resection surgery complete.

• Histologic or pathologic reports must verify either:

  • No tumour contacting the inked margin of surgically removed tissue, or
  • Focal involvement (<2mm front) if the margin is at the deep (posterior part) of the breast and the surgeon confirms that surgery extended to the deep fascia, or
  • Focal involvement (<2mm front) if the margin is superficial (anterior part of the breast or subcutaneous) and the surgeon confirms that surgery extended to the subcutis NB: In the case of focally involved deep or superficial margins, the medical records or multidisciplinary meeting notes or correspondence from the surgeon must indicate that the surgeon confirms the surgery extended to the deep fascia or subcutis as appropriate. Patients should routinely receive a lumpectomy bed boost in the conserved breast setting if there is focal superficial or focal deep involvement as defined above.
• Tumour oestrogen receptor and/or progesterone receptor positive (≥10% cells positive).
• Radiotherapy not yet commenced
• Planned radiotherapy dose prescribed to ICRU reference points in the irradiated breast / chest wall volumes at least the biological equivalent of 45 Gy in 25 fractions or more. (BED Gy4 ≥ 65, BED Gyx=D(1+n/x) where D=total dose, n=dose per fraction, x=alpha beta ratio, Gy4 selected as appropriate alpha-beta ratio for human breast cancer lines)
• An ECOG performance status score of 2 or less.

• Female and post menopausal shown by satisfying at least one of the following criteria (as per the ATAC study criteria16):

  • bilateral oophorectomy
  • age greater than 60
  • age 45-59 years with intact uterus and amenorrhoeic at least 12 months
  • Amenorrhoeic less than 12 months with follicle stimulating hormone (FSH) levels within the post menopausal range (including patients with amenorrhoea due to chemotherapy, LHRH use or who have had hormone replacement following hysterectomy) Note: it is recommended for women under the age of 45 who have been rendered menopausal by chemotherapy that they be enrolled onto the strata which switches to Tamoxifen after the initial 3 months of anastrozole.
• Is not receiving chemotherapy, or is receiving chemotherapy but the course will be completed at least 3 weeks prior to commencing radiotherapy
• Unilateral treatment
• Has provided written informed consent for participation in this trial

Exclusion Criteria:

• Previous radiotherapy to the area to be treated
• Previous invasive malignancy within 5 years of current breast cancer diagnosis with the exception of cervix in-situ or skin cancer other than melanoma.
• Patients with clinical evidence of metastatic disease.
• Previous hormonal breast cancer therapy.
• Ongoing hormone replacement therapy

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Concurrent; Investigational treatment: Anastrozole commenced before (Pre-radiotherapy commencement of anastrozole) and continued during radiotherapy.	Drug: Pre-radiotherapy commencement of anastrozole; Anastrozole: 1mg per day will be prescribed for 12 weeks. Commencing within 1 week of randomisation, to be administered from a min of 1 week before and a max of 4 weeks before commencement of radiotherapy and continued throughout radiotherapy. After 12 weeks administration of anastrozole according to trial regimen, anastrozole can be continued at the treating clinician's discretion and in accordance with the preference selected at the time of randomisation and stratification. The alternative options to long-term anastrozole are tamoxifen or cessation of anti-oestrogen therapy.; Other Names: Arimidex; Radiation: Radiotherapy; Radiotherapy must commence within 1 month of randomisation. Radiotherapy planning and treatment is as per the protocol.; Other Names: RT, Radiation Therapy
Active Comparator: Arm B: Sequential; Standard Treatment: Anastrozole and subsequent anti-oestrogen therapy delayed until after radiotherapy (Post radiotherapy commencement of anastrozole)	Radiation: Radiotherapy; Radiotherapy must commence within 1 month of randomisation. Radiotherapy planning and treatment is as per the protocol.; Other Names: RT, Radiation Therapy; Drug: Post radiotherapy commencement of anastrozole; Anastrozole 1mg per day will be prescribed for 12 weeks after radiotherapy is completed. Anastrozole should commence within 1 week of the last fraction of radiotherapy and be continued for a total of 12 weeks. After 12 weeks administration according to the trial regimen, any subsequent hormone therapy is as for the concurrent arm.; Other Names: Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine if commencement of anastrozole prior to radiotherapy results in improved local control compared to anastrozole commenced after radiotherapy.	10 years post radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Rates of distant failure	10 years post radiotherapy
Overall Survival	10 years post radiotherapy
Normal tissue complications	10 years post radiotherapy
Cosmesis	10 years post radiotherapy

Collaborators and Investigators

• Sponsor: Trans Tasman Radiation Oncology Group
• Investigators: Study Chair: Peter Graham, MBBS, Trans Tasman Radiation Oncology Group

Publications and helpful links

General Publications

• Browne LH, Graham PH. Good intentions and ICH-GCP: Trial conduct training needs to go beyond the ICH-GCP document and include the intention-to-treat principle. Clin Trials. 2014 Dec;11(6):629-34. doi: 10.1177/1740774514542620. Epub 2014 Jul 14.

Helpful Links

• Link to the TROG website where trial information can be found.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2009
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: April 23, 2009
• First Submitted That Met QC Criteria: April 23, 2009
• First Posted (Estimate): April 24, 2009

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; Timing of Radiotherapy; Local control
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Anastrozole
• Other Study ID Numbers: TROG 08.06; ACTRN12610000307000 (Registry Identifier: ANZCTR)