Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer.

• Register: EUCTR
• Last refreshed on: 5 August 2014
• Main ID: EUCTR2013-003839-30-ES
• Date of registration: 08/05/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer.
• Scientific title: A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. - Olympia
• Date of first enrolment: 24/07/2014
• Target sample size: 1320
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003839-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

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

Contacts

• Name: Information Center
• Affiliation: AstraZeneca Farmaceutica Spain, S.A.

• Name: Information Center
• Affiliation: AstraZeneca Farmaceutica Spain, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically confirmed non-metastatic primary triple negative invasive adenocarcinoma of the breast.
-Invasive TNBC
-Documented 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 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 660
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 660

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 cancer, EXCEPTIONS: 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, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ? 5 years prior to randomization. More than one course of chemotherapy for previous malignancies.
-Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc ?470 msec.
- Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.-Whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adjuvant breast cancer
MedDRA version: 17.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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 invasive breast primary cancer and/or new epithelial ovarian cancer.
- Efficacy of olaparib on patient reported outcomes using the FACIT fatigue scale and EORTC QLQ-C30 QoL scale.
- 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).

Timepoint(s) of evaluation of this end point: Recurrent/new cancers assessments 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.

Main Objective: Efficacy of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS).

Primary end point(s): Invasive Disease Free Survival (IDFS)

Secondary Outcome(s)

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

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 invasive breast primary cancer and/or new epithelial ovarian cancer.
4. Efficacy of olaparib on patient reported outcomes using the FACIT fatigue scale and EORTC QLQ-C30 QoL scale.
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).

Secondary ID(s)

BIG 6-13

D081CC00006

2013-003839-30-GB

Source(s) of Monetary Support

AstraZeneca AB