Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000506099
Ethics application status
Approved
Date submitted
27/05/2010
Date registered
18/06/2010
Date last updated
17/09/2023
Date data sharing statement initially provided
3/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
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
Scientific title
Women over 18 years with Triple Negative (oestrogen receptor alpha negative, progesterone receptor negative, HER-2 negative) but Oestrogen Receptor Beta Positive Metastatic Breast Cancer will be treated with Tamoxifen to assess the efficacy of this treatment
Secondary ID [1] 283174 0
ANZ 1001
Universal Trial Number (UTN)
Trial acronym
SORBET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple Negative Metastatic Breast Cancer 257216 0
Condition category
Condition code
Cancer 257356 257356 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To assess the efficacy of tamoxifen 20 mg (oral tablet) daily in triple negative (oestrogen receptor alpha negative, progesterone receptor negative, HER-2 negative) but oestrogen receptor beta positive metastatic breast cancer. Tamoxifen will be administered for duration of the trial (no set time limit - patients will continue to take tamoxifen until progression, withdrawal of consent or unacceptable toxicity).
Intervention code [1] 256336 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 258256 0
Overall response rate to tamoxifen defined as the proportion of all patients on study who commenced tamoxifen and who satisfy the Reponse Evaluation Criteria In Solid Tumours (RECIST1.1) criteria for either a complete response or partial response
Timepoint [1] 258256 0
RECIST evaluated at baseline and then every 8 weeks for the duration of the trial (patients will continue being on study until progression, withdrawal of consent or unacceptable toxicity). It is anticipated that patient accrual will take approx. 4 years for this study.
Secondary outcome [1] 263913 0
Progression free survival, defined as the duration of time from registration to time of progression, will be displayed using Kaplan-Meier survival curves.
Timepoint [1] 263913 0
RECIST evaluated at baseline and then every 8 weeks for the duration of the trial (patients will continue being on study until progression, withdrawal of consent or unacceptable toxicity). It is anticipated that patient accrual will take approx. 4 years for this study.
Secondary outcome [2] 263914 0
Clinical benefit rate (complete response or partial response or stable disease for 24 weeks). The Clinical Benefit Rate, defined as CR + PR + SD for 24 weeks, will be calculated after completion of the second stage of the study expected to be 12 months after the last patient starts treatment. A 95% confidence interval will also be reported
Timepoint [2] 263914 0
The clinical benefit rate, defined as CR + PR + SD for 24 weeks, will be calculated after completion of the second stage of the study expected to be 12 months after the last patient starts treatment.

Eligibility
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. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be recruited from investigator’s clinical practices. Patients will sign a ‘consent to screen’ form at the pre-registration step. A separate written informed consent must also be signed by the patient and investigator prior to registration.

All patients in this trial will be started on the same dose and schedule of tamoxifen. No dose reductions will be permitted. Following registration, patients must begin protocol treatment within 72 hours.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Nil
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
30/07/2010
Actual
14/03/2011
Date of last participant enrolment
Anticipated
31/01/2015
Actual
28/11/2013
Date of last data collection
Anticipated
22/08/2014
Actual
22/08/2014
Sample size
Target
66
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment outside Australia
Country [1] 2595 0
New Zealand
State/province [1] 2595 0

Funding & Sponsors
Funding source category [1] 256840 0
Other Collaborative groups
Name [1] 256840 0
Australia and New Zealand Breast Cancer Trials Group
Country [1] 256840 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia and New Zealand Breast Cancer Trials Group
Address
ANZBCTG Trials Coordination Department PO Box 155 Hunter Region Mail Centre NSW 2310
Country
Australia
Secondary sponsor category [1] 256117 0
None
Name [1] 256117 0
Address [1] 256117 0
Country [1] 256117 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258857 0
Peter MacCallum Cancer Center HREC
Ethics committee address [1] 258857 0
Ethics committee country [1] 258857 0
Date submitted for ethics approval [1] 258857 0
01/06/2010
Approval date [1] 258857 0
24/09/2010
Ethics approval number [1] 258857 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31074 0
Prof John F. Forbes
Address 31074 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 31074 0
Australia
Phone 31074 0
+61 2 4925 5235
Fax 31074 0
Email 31074 0
[email protected]
Contact person for public queries
Name 14321 0
John F. Forbes
Address 14321 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 14321 0
Australia
Phone 14321 0
+61 2 4925 3068
Fax 14321 0
+ 61 2 4985 0141
Email 14321 0
[email protected]
Contact person for scientific queries
Name 5249 0
Professor John F Forbes, Director of Research
Address 5249 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 5249 0
Australia
Phone 5249 0
+61 2 4925 3068
Fax 5249 0
+ 61 2 4985 0141
Email 5249 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymised Individual Patient Data (IPD) collected during the trial.
When will data be available (start and end dates)?
Data will be made available for request after publication of the main/final study results; no end date.

Note that there may be additional circumstances preventing BCT from sharing requested data as outlined in the BCT Data Sharing Guidelines.
Available to whom?
Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Refer to the BCT Data Sharing Guidelines
Available for what types of analyses?
To achieve the aims in the approved proposal.
How or where can data be obtained?
Subject to approval by Breast Cancer Trials [email protected] (refer to BCT Data Sharing Guidelines).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18779Other https://researchdata.edu.au/health/view/2538189  Please refer to BCT Data Sharing Guidelines attach... [More Details] 335395-(Uploaded-18-08-2023-13-39-32)-Study-related document.pdf
20376Study protocol https://doi.org/10.58080/fhk5-ka87 
20377Data dictionary https://doi.org/10.58080/fhk5-ka87 



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.