STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing)

Sponsor

Trans Tasman Radiation Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00887380

Collaborator

(none)

2,023

Enrollment

Locations

Arms

182.5

Anticipated Duration (Months)

59.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Pre-radiotherapy commencement of anastrozole Radiation: Radiotherapy Drug: Post radiotherapy commencement of anastrozole	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

2023 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Sep 16, 2009

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Canberra Hospital	Canberra	Australian Capital Territory	Australia	2605
2	Campbelltown Hospital	Campbelltown	New South Wales	Australia	2560
3	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
4	Genesis Cancer Care Hurstville	Hurstville	New South Wales	Australia	2220
5	St George Hospital	Kogarah	New South Wales	Australia	2217
6	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
7	Calvary Mater Newcastle	Newcastle	New South Wales	Australia	2298
8	Central West Cancer Service	Orange	New South Wales	Australia
9	Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
10	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
11	Riverina Cancer Centre	Wagga Wagga	New South Wales	Australia	2650
12	Illawarra Cancer Care Centre	Wollongong	New South Wales	Australia	2500
13	Alan Walker Cancer Centre	Darwin	Northern Territory	Australia	811
14	Genesis Cancer Care	Auchenflower	Queensland	Australia	4066
15	Cairns ROQ	Cairns	Queensland	Australia	4350
16	Genesis Cancer Care	Chermside	Queensland	Australia	4032
17	The Townsville Hospital	Douglas	Queensland	Australia	4810
18	Radiation Oncology Gold Coast	Gold Coast	Queensland	Australia	4217
19	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
20	Radiation Oncology - Mater Centre	South Brisbane	Queensland	Australia	4101
21	Genesis Southport	Southport	Queensland	Australia
22	St Andrew's Toowoomba Hospital	Toowoomba	Queensland	Australia	4350
23	Genesis Care	Tugun	Queensland	Australia	4224
24	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
25	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
26	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
27	Geelong Hospital	Geelong	Victoria	Australia	3220
28	Genesis Cancer Care	Bunbury	Western Australia	Australia
29	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
30	Royal Perth Hospital	Perth	Western Australia	Australia	6001
31	Perth Radiation Oncology	Wembley	Western Australia	Australia	6014
32	Auckland Hospital	Auckland		New Zealand
33	Christchurch Hopsital Oncology Sevice	Christchurch		New Zealand
34	Palmerston North	Palmerston North		New Zealand