OPTIMA / BCT 2202
Optimal personalised treatment of early breast cancer using multiparameter analysis
Trial summary:
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.
Receptor status / problem studied:
Inclusion criteria
Current participant inclusion criteria (amended 20/10/2020) and added 14/02/2024:
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 (>10% of tumour cells stained positive) as determined by the referring site in a laboratory meeting national external quality assurance standards and in accordance with national or ASCO-CAP guidelines (83).
4) HER2 negative (IHC 0-1+, or ISH negative/non-amplified) as determined by the referring site in a laboratory meeting national external quality assurance standards and in accordance with national or ASCO-CAP guidelines (84).
5) Tumour size and axillary lymph node status; one of the following must apply:
|— a) 4-9 lymph nodes involved AND any invasive tumour size.
|— b) 1-3 nodes involved, with at least 1 node containing a macrometastasis (i.e. deposit >2mm diameter) AND any invasive tumour size.
|— c) 1-3 lymph nodes involved with micrometastases only (i.e. deposit >0.2-2mm diameter) AND invasive tumour size ≥ 20mm.
|— d) Node negative AND invasive tumour size ≥ 30mm.
6) Considered appropriate for adjuvant chemotherapy by the 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) Multiple ipsilateral cancers are permitted provided at least one tumour fulfils the tumour size and axillary lymph node entry criteria, and none meet any of the exclusion criteria.
9) Bilateral cancers are permitted provided the tumour(s) in one breast meets the eligibility criteria and the other, contralateral tumour is not ER negative and/or HER2 positive and not clinically significant.
10) Short term pre-surgical treatment with endocrine therapy including in combination with non-cytotoxic agents is allowed providing that the duration of treatment does not exceed 8 weeks.
11) Informed consent for the study.
Exclusion criteria
Current participant exclusion criteria (amended 17/09/2022) and added 14/02/2024:
1) ≥10 involved axillary lymph nodes (with either macrometastases and/ or micrometastases) or involvement of any of internal mammary, supraclavicular and infraclavicular nodes.
|— a) NOTE: Internal mammary lymph nodes identified by anatomical imaging studies alone will be considered uninvolved where the diameter is <10mm.
2) ER negative/low OR HER2 positive/amplified tumour (as determined by the referring site).
3) Metastatic disease.
4) Previous diagnosis of malignancy unless:
|— a) Managed by local treatment only AND disease-free for 10 years.
|— b) Ductal carcinoma in situ (DCIS) or pleomorphic lobular carcinoma in situ (pleomorphic LCIS) of the breast managed by local treatment only; treatment with anti-oestrogens is not permitted.
|— c) Any other in situ carcinoma as defined by the International Classification of Diseases for Oncology (ICD-O) including basal cell carcinoma of skin and cervical intraepithelial neoplasia.
5) Pre-operative anti-cancer treatments except short-term endocrine therapy administered as per the inclusion criteria.
6) Adjuvant systemic treatment commenced prior to trial entry* except endocrine therapy, which must be discontinued prior to starting trial-allocated chemotherapy.
7) Treatment with agents, including ovarian suppression, known to influence breast cancer growth but prescribed for other indications within one year of trial entry* except as follows:
8) Use of oestrogen replacement therapy (HRT) provided this is stopped before surgery.
9) Drugs administered for in vitro fertilization or fertility preservation.
10) Use of hormonal contraception.
11) Trial entry* and randomisation more than 12 weeks after completion of breast cancer surgery. Trial entry should ordinarily be within 8 weeks of final surgery.
12) Planned further surgery for breast cancer, including axillary surgery, to take place after trial entry*, except either re-excision or completion mastectomy for close or positive/involved margins which may be undertaken following completion of chemotherapy if given.
Trial Title
OPTIMA / BCT 2202
Diagnosis
Breast cancer
Type of trial
Collaborative
Type of treatement
Medical Oncology
Phase
Registry