STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing)

NCT ID: NCT00887380

Last Updated: 2022-11-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 2023 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-16
• Study Completion Date: 2024-12-31

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%.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Concurrent

Investigational treatment: Anastrozole commenced before (Pre-radiotherapy commencement of anastrozole) and continued during radiotherapy.

Group Type: ACTIVE_COMPARATOR

Pre-radiotherapy commencement of anastrozole

Intervention Type: DRUG

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.

Radiotherapy

Intervention Type: RADIATION

Radiotherapy must commence within 1 month of randomisation. Radiotherapy planning and treatment is as per the protocol.

Arm B: Sequential

Standard Treatment: Anastrozole and subsequent anti-oestrogen therapy delayed until after radiotherapy (Post radiotherapy commencement of anastrozole)

Group Type: ACTIVE_COMPARATOR

Radiotherapy

Intervention Type: RADIATION

Radiotherapy must commence within 1 month of randomisation. Radiotherapy planning and treatment is as per the protocol.

Post radiotherapy commencement of anastrozole

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Radiotherapy

Radiotherapy must commence within 1 month of randomisation. Radiotherapy planning and treatment is as per the protocol.

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Other Intervention Names

Arimidex; RT, Radiation Therapy; Arimidex

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Graham, MBBS

Role: STUDY_CHAIR

Trans Tasman Radiation Oncology Group

Locations

The Canberra Hospital

Canberra, Australian Capital Territory, Australia

Campbelltown Hospital

Campbelltown, New South Wales, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Genesis Cancer Care Hurstville

Hurstville, New South Wales, Australia

St George Hospital

Kogarah, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Central West Cancer Service

Orange, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Riverina Cancer Centre

Wagga Wagga, New South Wales, Australia

Illawarra Cancer Care Centre

Wollongong, New South Wales, Australia

Alan Walker Cancer Centre

Darwin, Northern Territory, Australia

Genesis Cancer Care

Auchenflower, Queensland, Australia

Cairns ROQ

Cairns, Queensland, Australia

Genesis Cancer Care

Chermside, Queensland, Australia

The Townsville Hospital

Douglas, Queensland, Australia

Radiation Oncology Gold Coast

Gold Coast, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Radiation Oncology - Mater Centre

South Brisbane, Queensland, Australia

Genesis Southport

Southport, Queensland, Australia

St Andrew's Toowoomba Hospital

Toowoomba, Queensland, Australia

Genesis Care

Tugun, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Geelong Hospital

Geelong, Victoria, Australia

Genesis Cancer Care

Bunbury, Western Australia, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Perth Radiation Oncology

Wembley, Western Australia, Australia

Auckland Hospital

Auckland, , New Zealand

Christchurch Hopsital Oncology Sevice

Christchurch, , New Zealand

Palmerston North

Palmerston North, , New Zealand

Countries

Australia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 25023199 (View on PubMed)

Related Links

http://www.trog.com.au

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

Other Identifiers

ACTRN12610000307000

Identifier Type: REGISTRY

Identifier Source: secondary_id

TROG 08.06

Identifier Type: -

Identifier Source: org_study_id