A single arm phase II study of the efficacy of tamoxifen in triple negative (oestrogen receptor alpha negative, progesterone receptor negative, HER-2 negative) but oestrogen receptor beta positive metastatic breast cancer (ANZ 1001 SORBET)

Funding

Other Collaborative groups,Australia and New Zealand Breast Cancer Trials Group

Scientific enquiries

Prof Professor John F Forbes, Director of Research

Brief Summary

This study looks at the effectiveness of the drug tamoxifen in treating breast cancer which is classified as triple negative (oestrogen receptor alpha negative, progesterone receptor negative, HER-2 negative) and oestrogen receptor beta positive, where the cancer has spread to distant sites (metastases). Who is it for? You can join this study if you are a woman with triple negative metastatic breast cancer that is oestrogen receptor beta positive and chemotherapy and/or radiotherapy is currently .... This study looks at the effectiveness of the drug tamoxifen in treating breast cancer which is classified as triple negative (oestrogen receptor alpha negative, progesterone receptor negative, HER-2 negative) and oestrogen receptor beta positive, where the cancer has spread to distant sites (metastases). Who is it for? You can join this study if you are a woman with triple negative metastatic breast cancer that is oestrogen receptor beta positive and chemotherapy and/or radiotherapy is currently not considered appropriate. Prior to entering the study, a sample of metastatic tumour must be tested and confirmed to be oestrogen receptor beta positive. Trial details Some breast cancer cells contain receptors which the female hormone oestrogen binds to, causing the cancer to grow. The study aims to find out whether tamoxifen may be useful for treating metastatic breast cancer that contains the oestrogen beta receptor. Tamoxifen is an anti-oestrogen drug which is frequently used to treat breast cancers that contain the oestrogen alpha receptor but has not been used specifically to treat breast cancers that contain the oestrogen beta receptor. Participants will all receive one oral tablet (20mg) of tamoxifen daily, unless they suffer unacceptable side effects, or their breast cancer progresses.
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Key Inclusion Criteria

1. Female patients, greater than or equal to 18 years with histologically or cytologically confirmed triple negative (oestrogen receptor alpha (ERa) absent, PgR (progesterone receptor) absent, Human Epidermal growth factor Receptor 2 (HER2) In situ hybridisaton (ISH) negative or immunohistochemistry ((IHC) 0 or 1)) breast cancer. All IHC results for ERa and PgR on all tumour specimens must not show any staining in the tumour (i.e. ERa and PgR absent staining in all tumour specimens). 2. Metastat .... 1. Female patients, greater than or equal to 18 years with histologically or cytologically confirmed triple negative (oestrogen receptor alpha (ERa) absent, PgR (progesterone receptor) absent, Human Epidermal growth factor Receptor 2 (HER2) In situ hybridisaton (ISH) negative or immunohistochemistry ((IHC) 0 or 1)) breast cancer. All IHC results for ERa and PgR on all tumour specimens must not show any staining in the tumour (i.e. ERa and PgR absent staining in all tumour specimens). 2. Metastatic disease for which, in the investigator’s opinion, chemotherapy and/or radiotherapy is currently not indicated. 3. Metastatic disease amenable to biopsy or previously biopsied. All patients must have a biopsy from a metastatic disease site, including patients presenting with de novo metastatic disease. A biopsy from axillary or supraclavicular nodes is acceptable for the following: a) Patients with no distant metastatic disease but with axillary or supraclavicular nodal disease that is considered incurable, either: i) Axillary nodes (ipsilateral or contralateral), that are measurable by RECIST and can be followed for response ii) Supraclavicular nodes (ipsilateral or contralateral) that are measurable by RECIST and can be followed for response. b) Patients with distant metastatic disease which is not amenable to biopsy Note that for a) part i) and b) the biopsy confirming triple negative, ER beta positive breast cancer in the axillary node must have occurred at a time point when the disease was considered incurable, i.e. the original pathology from initial sentinel node biopsy or axillary dissection undertaken as part of curative therapy is NOT acceptable. 4. ER beta positive in the metastatic breast cancer sample. (ERbeta1 will be measured with IHC and nuclear ERbeta1 staining with Allred score >3 defined as positive). 5. At least one measurable lesion as defined by revised Response Evaluation Criteria in Solid Tumours 1.1 (RECIST) (at least one lesion that can be accurately measured in at least one dimension with longest diameter to be recorded as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT scan). Measurable lesions in a previously irradiated field are excluded unless progression in the lesion post radiotherapy is documented according to RECIST criteria on the CT scan. 6. At the time of registration, patients must fulfill one of the following: a) Disease is currently progressing - last administration of systemic anti-cancer therapy for metastatic disease (if given) must have ceased greater than or equal to 21 days prior to registration. OR b) Disease is currently not progressing - last administration of systemic anti-cancer therapy for metastatic disease (if given) must have ceased greater than or equal to 42 days prior to registration. 7. Life expectancy of 12 weeks or more. 8. Eastern cooperative oncology group (ECOG)performance status less than or equal to 2. 9. Provision of written informed consent.
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Key Exclusion Criteria

1. Patients with any positive staining for ERa and/or PgR in ANY sample of invasive breast cancer (including any biopsy of earlier stage disease). 2. Rapidly progressive metastatic disease which, in the investigator’s opinion is not suitable for endocrine therapy. 3. Last dose of chemotherapy < 21 days before the start of tamoxifen. Patients must not have concurrent chemotherapy and tamoxifen. 4. Treatment with an investigational drug < 21 days prior to registration. 5. Only measurable lesions i .... 1. Patients with any positive staining for ERa and/or PgR in ANY sample of invasive breast cancer (including any biopsy of earlier stage disease). 2. Rapidly progressive metastatic disease which, in the investigator’s opinion is not suitable for endocrine therapy. 3. Last dose of chemotherapy < 21 days before the start of tamoxifen. Patients must not have concurrent chemotherapy and tamoxifen. 4. Treatment with an investigational drug < 21 days prior to registration. 5. Only measurable lesions in a previously irradiated field without evidence of progression. 6. Patients who have had previous hormonal therapy for breast cancer (includes Selective Oestrogen Receptor Modulators and Aromatase Inhibitors). 7. Newly diagnosed or uncontrolled intracerebral metastases. Previously treated, asymptomatic brain metastases are permissible; patients must be stable and off steroid therapy and have a life expectancy of at least 12 weeks. 8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to tamoxifen. 9. Receiving any medications or substances that are inhibitors or inducers of CYP3A4 and CYP2D6. 10. Previous or concomitant invasive malignancy (except breast cancer). The exceptions are: a) patients with non-breast malignancy greater than or equal to10 years ago, treated with curative intent and without evidence of recurrence b) basal or squamous cell carcinoma of the skin c) in situ carcinoma without invasion (includes in situ breast carcinoma) d) the following non-breast invasive malignancy diagnosed greater than or equal to 5 years ago and without recurrence: i) stage I papillary thyroid cancer ii)stage Ia carcinoma of the cervix iii) borderline or stage I ovarian cancer iv) superficial bladder cancer 11. Psychiatric illness/social situations that would limit compliance with study requirements. 12. Pregnancy or breast feeding (women of child-bearing potential must agree to use adequate non-hormonal contraception). A serum or urine test must be carried out on all women of child-bearing potential to exclude pregnancy. 13. Patients with a history of thrombosis should only participate if considered medically suitable by their doctor.
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