STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing)

Trans Tasman Radiation Oncology Group

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Post radiotherapy commencement of anastrozole; Drug: Pre-radiotherapy commencement of anastrozole; Radiation: Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00887380

TROG 08.06

ACTRN12610000307000 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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%.

Enrollment: 2,023 patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,023 participants in 2 patient groups

Arm A: Concurrent

Active Comparator group

Description:

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

Treatment:

Radiation: Radiotherapy

Drug: Pre-radiotherapy commencement of anastrozole

Arm B: Sequential

Active Comparator group

Description:

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

Treatment:

Radiation: Radiotherapy

Drug: Post radiotherapy commencement of anastrozole