Clinical trial NCT00887380: STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Breast Cancer
Timing of Radiotherapy
Local control
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
First posted: 2009-04-24
Enrollment: 2023
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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%.

Eligibility criteria: 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

Primary outcomes:
measure: To determine if commencement of anastrozole prior to radiotherapy results in improved local control compared to anastrozole commenced after radiotherapy.
timeFrame: 10 years post radiotherapy
Secondary outcomes:
measure: Rates of distant failure
timeFrame: 10 years post radiotherapy
measure: Overall Survival
timeFrame: 10 years post radiotherapy
measure: Normal tissue complications
timeFrame: 10 years post radiotherapy
measure: Cosmesis
timeFrame: 10 years post radiotherapy
Other outcomes:
Locations:
city: Canberra
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Hurstville
country: Australia
facility: Genesis Cancer Care Hurstville
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Orange
country: Australia
facility: Central West Cancer Service
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Centre
state: New South Wales
city: Wollongong
country: Australia
facility: Illawarra Cancer Care Centre
state: New South Wales
city: Darwin
country: Australia
facility: Alan Walker Cancer Centre
state: Northern Territory
city: Auchenflower
country: Australia
facility: Genesis Cancer Care
state: Queensland
city: Cairns
country: Australia
facility: Cairns ROQ
state: Queensland
city: Chermside
country: Australia
facility: Genesis Cancer Care
state: Queensland
city: Douglas
country: Australia
facility: The Townsville Hospital
state: Queensland
city: Gold Coast
country: Australia
facility: Radiation Oncology Gold Coast
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Radiation Oncology - Mater Centre
state: Queensland
city: Southport
country: Australia
facility: Genesis Southport
state: Queensland
city: Toowoomba
country: Australia
facility: St Andrew's Toowoomba Hospital
state: Queensland
city: Tugun
country: Australia
facility: Genesis Care
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Geelong
country: Australia
facility: Geelong Hospital
state: Victoria
city: Bunbury
country: Australia
facility: Genesis Cancer Care
state: Western Australia
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Wembley
country: Australia
facility: Perth Radiation Oncology
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hopsital Oncology Sevice
city: Palmerston North
country: New Zealand
facility: Palmerston North
Study officials:
affiliation: Trans Tasman Radiation Oncology Group
name: Peter Graham, MBBS
role: STUDY_CHAIR
References:
citation: 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.