Condition category
Cancer
Date applied
26/06/2012
Date assigned
26/06/2012
Last edited
01/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Miss Amy Campbell

ORCID ID

Contact details

Warwick Clinical Trials Unit
Warwick Medical School
The University of Warwick
Coventry
CV4 7AL
United Kingdom
-
a.f.campbell@warwick.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Protocol number: 11/0479; UKCRN ID: 12255; funder project numbers: HTA 10/34/01, HTA 10/34/501

Study information

Scientific title

Optimal Personalised Treatment of early breast cancer using Multiparameter Analysis: a randomised study

Acronym

OPTIMA

Study hypothesis

The OPTIMA trial seeks to advance the development of personalised medicine in breast cancer by using multi-parameter tests to identify those women who are likely to benefit from chemotherapy and sparing those who are unlikely to benefit from an unnecessary and unpleasant treatment. The OPTIMA study population would ordinarily be treated with a combination of chemotherapy and endocrine therapy. The trial compares the management of patients using test-directed assignment to chemotherapy with standard management (chemotherapy) in a non-inferiority design. OPTIMA prelim is the preliminary phase of the study which will select the testing technology to be used in the main trial and demonstrate whether the main trial is feasible.

Preliminary study objectives:
1. To evaluate the performance and health-economics of alternative multiparameter tests to determine which technology(s) should be evaluated in the main trial.
2. To establish the acceptability to patients and clinicians of randomisation to test-directed treatment assignment.
3. To establish efficient and timely sample collection and analysis essential to the delivery of multi-parameter test driven treatment.

Main trial objectives:
1. To identify a method of selection that reduces chemotherapy use for patients with hormone sensitive primary breast cancer without detriment to recurrence and survival.
2. To establish the cost-effectiveness of test-directed treatment strategies compared to standard practice.

More details can be found at http://www.nets.nihr.ac.uk/projects/hta/103401 and http://www.nets.nihr.ac.uk/projects/hta/1034501

Ethics approval

South East Coast - Surrey, 22/06/2012, ref: 12/LO/0515

Study design

Randomised; Interventional; Design type: Diagnosis

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Breast Cancer; Disease: Breast

Intervention

Control: Chemotherapy followed by endocrine therapy
Experimental: Test directed assignment of chemotherapy or not, followed by endocrine therapy
Follow up length: 10 years

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

OPTIMA prelim:
1. Identification of a multi-parameter test technology that is suitable for validation in the main study.
2. Recruitment of 300 patients in not more than 2 years from the first centre opening to recruitment, and, for the final 150 patients:
2.1. Patient acceptance rate will be at least 40%
2.2. Recruitment will take no longer than 6 months
2.3. Chemotherapy will start within 6 weeks of signing the OPTIMA consent form for no less than 85% of chemotherapy assigned patients.

Main trial:
1. Invasive disease free survival (IDFS) non-inferiority of test-directed chemotherapy treatment and endocrine therapy compared to chemotherapy followed by endocrine treatment
2. Cost effectiveness evaluation of protocol specified multi-parameter assay driven treatment against standard clinical practice

Secondary outcome measures

Current secondary outcome measures as of 29/09/2015:
Main trial:
1. Distant disease free survival (DDFS)
2. Breast cancer specific survival (BCSS) and Overall survival (OS)
3. IDFS for patients with low risk patients with low-risk tumours
4. Quality of life and health resource use as measured by EQ-5D & FACT-B
5. Patient compliance with long term endocrine therapy

Previous secondary outcome measures:
Main trial:
1. Quality of life and health resource use as measured by EQ-5D & FACT-B
2. Distant disease free survival
3. Comparative performance of multi-parameter assays (if more than one adopted)
4. Patient compliance to long term endocrine therapy
5. Overall survival (OS)

Overall trial start date

01/07/2012

Overall trial end date

30/09/2023

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 29/09/2015:
1. Female or male, age >= 40
2. Excised invasive breast cancer with local treatment either completed or planned according to trial guidelines.
3. ER positive (Allred score >=3 or H-score >=10 or >1% of tumour cells stained positive) as determined by the referring site (in a laboratory meeting NEQAS standards).
4. HER2 negative (IHC 0-1+, or ISH negative/non-amplified (ratio of HER2/chromosome 17 <2.00 and copy number <6)) as determined by the referring site (in a laboratory meeting NEQAS standards).
5. Axillary lymph node status:
5.1. 1-9 involved (macrometastases i.e. >2mm) OR
5.2. Node negative AND tumour size >= 30mm.
Nodes containing micrometastases (i.e. >0.2-2mm) or isolated tumour cell clusters (ITC) only (i.e. <=0.2mm) will be considered to be uninvolved.
6. Considered appropriate for adjuvant chemotherapy by treating physician.
7. Patient must be fit to receive chemotherapy and other trial-specified treatments with no concomitant medical, psychiatric or social problems that might interfere with informed consent, treatment compliance or follow up.
8. Bilateral cancers are permitted provided at least one tumour fulfils the entry criteria and none meet any of the exclusion criteria.
9. Multiple ipsilateral cancers are permitted provided at least one tumour fulfils the entry criteria and none meet any of the exclusion criteria.
10. Written informed consent for the study.

Previous inclusion criteria:
1. Female, age >= 40
2. Excised invasive breast cancer with local treatment either completed or planned according to trial guidelines.
3. Estrogen Receptor (ER) +ve (Allred score >=3 or Hscore >=10 or as otherwise established by the reporting pathologist) as determined by the referring centre and centrally confirmed.
4. Human epidermal growth factor receptor 2 (HER2) negative - i.e. IHC 0-1+, or FISH or other ISH nonamplified (HER2 testing in lab meeting NEQAS EQA standards), as determined by the referring centre and centrally confirmed.
5. Axillary lymph node status:
5.1. 1-9 involved (macro metastases i.e. >2mm OR micro metastases i.e. >0.22mm) OR
5.2. Node negative AND tumour size > 30mm. Nodes containing isolated tumour cell clusters (ITC) only, i.e. <=0.2mm diameter, will be considered to be uninvolved.
6. Considered appropriate for adjuvant chemotherapy by treating physician
7. Patient must be fit to receive chemotherapy and other trialspecified treatments with no concomitant medical, psychiatric or social problems that might interfere with informed consent, treatment compliance or follow up
8. Bilateral and multifocal cancers are permitted provided at least one tumour fulfils the entry criteria and none meet any of the exclusion criteria (pathology information must be available for at least 2 tumours).
9. Negative staging if either clinical suspicion of metastatic disease or high risk (pT >50mm or >=4 involved nodes)
10. Written informed consent for the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

OPTIMA prelim : 300 (plus 200 extension), main trial: 4500

Participant exclusion criteria

Current exclusion criteria as of 29/09/2015:
1. >=10 involved axillary nodes (as defined in the inclusion criteria) or involved internal mammary node.
2. ER negative OR HER2 positive/amplified (as determined by the referring site).
3. Metastatic disease.
4. Previous diagnosis of malignancy unless:
4.1. Managed by surgical treatment only and disease free for 10 years
4.2. Previous basal cell carcinoma of skin, cervical intraepithelial neoplasia or ductal carcinoma in situ (DCIS) of the breast treated with surgery only or previous diagnosis of lobular carcinoma in situ (LCIS).
5. The use of oestrogen replacement therapy (HRT) at the time of surgery. Patients who are taking HRT at the time of diagnosis are eligible provided the HRT is stopped before surgery.
6. Pre-surgical chemotherapy, endocrine therapy or radiotherapy for breast cancer. Treatment with endocrine agents known to be active in breast cancer including ovarian suppression is permitted provided this was completed >1 year prior to study entry.
7. Commencement of adjuvant treatment prior to trial entry. Short-term endocrine therapy initiated because of, for instance, prolonged recovery from surgery is permitted but must be discontinued at trial entry.
8. Trial entry more than 8 weeks after completion of breast cancer surgery.
9. Planned further surgery for breast cancer, including axillary surgery, to take place after randomisation, except either re-excision or completion mastectomy for close or positive/involved margins which may be undertaken following completion of chemotherapy.
10. Patients with more than two involved axillary nodes (as defined in the inclusion criteria) identified by sentinel node biopsy or by axillary sampling where further axillary surgery is not planned.

Previous exclusion criteria:
1. >=10 involved axillary nodes or involved internal mammary node
2. ER -ve OR HER2 positive/amplified on central eligibility testing
3. Previous diagnosis of malignancy unless:
3.1. Managed by surgical treatment only and disease free for 10 years or
3.2. Previous basal cell carcinoma of skin, cervical intraepithelial neoplasia or in situ ductal carcinoma of the breast treated with surgery only
4. The use of estrogen replacement therapy (HRT) at the time of surgery. Patients who are taking HRT at the time of diagnosis are eligible provided the HRT is stopped before the day of surgery
5. Previous chemotherapy, endocrine therapy or radiotherapy for breast cancer. Treatment with endocrine agents known to be active in breast cancer including ovarian suppression is permitted provided this was completed >1 year prior to study entry
6. Planned further surgery for breast cancer other than either re-excision or completion mastectomy for close margins this may be undertaken following completion of chemotherapy
7. Patients with more than two involved axillary nodes (as defined in the inclusion criteria) identified by sentinel node biopsy or by axillary sampling who have not undergone further axillary surgery

Recruitment start date

01/07/2012

Recruitment end date

30/09/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Warwick Clinical Trials Unit
Warwick Medical School The University of Warwick
Coventry
CV4 7AL
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Joint Research Office
Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/26867046

Publication citations

Additional files

Editorial Notes

01/11/2016: Publication reference added. 29/09/2015: The following changes were made to the trial record: 1. The overall trial end date was changed from 30/04/2014 to 30/09/2023. 2. The target number of participants was changed from 300 to 'OPTIMA prelim : 300 (plus 200 extension), Main trial: 4500'