Adjuvant breast cancer MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -18 years old and older - Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast that is one of the following phenotypes: a)TNBC ER and PgR negative AND HER2 negative (not eligible for anti-HER2 therapy) b) ER and/or PgR positive, HER2 negative ER and/or PgR positive AND HER2 negative (not eligible for anti-HER2 therapy) -Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). - Completed adequate breast and axilla surgery. - Completed at least 6 cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or the combination of both. Prior platinum as potentially curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant treatment for breast cancer is allowed. -ECOG 0-1. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 500
Exclusion criteria
Exclusion criteria: - Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment. - Patients with second primary malignancy. EXCEPTIONS are: a) adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma b) other solid tumours and lymphomas (without bone marrow involvement) diagnosed = 5 years prior to randomisation and treated with no evidence of disease recurrence and for whom no more than one line of chemotherapy was applied. - Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. -Whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing - Evidence of metastatic breast cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS).;Secondary Objective: - Efficacy of adjuvant treatment with olaparib on overall survival (OS). - Efficacy of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS) - Efficacy of adjuvant treatment with olaparib on the incidence of new primary contralateral breast cancers (invasive and non-invasive), new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer - Efficacy of olaparib on patient reported outcomes using the FACIT Fatigue and EORTC QLQ-C30 QoL questionnaires. - Efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis). - Determine exposure to Olaparib (in plasma) in patients receiving Olaparib as adjuvant therapy;Primary end point(s): Invasive Disease Free Survival (IDFS);Timepoint(s) of evaluation of this end point: Recurrent/new cancers assessments will be performed at day 1, weeks 12, 24, 38, 52, premature study treatment discontinuation and 30-day follow-up visits. In follow-up period in year 2 every 3 months, in year 3, 4,5 every 6 months and year 6 to 10 every 12 months. MRI to be performed every 12 months after the 6 months scan. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Efficacy of adjuvant treatment with olaparib on overall survival (OS). 2. Efficacy of adjuvant treatment with olaparib on Distant Disease Free Survival (DDFS) 3. Efficacy of adjuvant treatment with olaparib on the incidence of new primary contralateral invasive breast cancer, primary contralateral non-invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal cancer 4. Efficacy of olaparib on patient reported outcomes using the FACIT Fatigue and EORTC QLQ-C30 QoL questionnaires. 5. Efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis). 6. Determine the exposure to olaparib (in plasma) in patients receiving olaparib as adjuvant therapy;Timepoint(s) of evaluation of this end point: 1. Day 1, 15, 29 week 8,12,16,20,24,38,52, 30 days after last dose of study medication, in year 2 every 3 months, in year 3, 4,5 every 6 months and above year 6 every 12 months 2 & 3.Physical examination will be performed at day 1, weeks 12, 24, 38, 52. In follow-up period in year 2 every 3 months, in year 3, 4,5 every 6 months and year 6 to 10 every 12 months. MRI to be performed every 12 months after the 6 months scan 4.EORTC QLQ-C30 and FACIT-Fatigue scale will be collected prior randomization, at weeks 24 and 52 and also every 6 months during the 2nd year post randomisation (months 18 and 24 only). 5. Within 15 years from last subject last visit 6. Visit 4, day 29 | — |
Countries
Argentina, Australia, Austria, Belgium, Canada, China, France, Germany, Hungary, Iceland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed