Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2negative primary breast cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Aug 2014 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-511096-15-00

EudraCT number

2013-003839-30

ClinicalTrials.gov

NCT02032823

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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

Secondary objectives 6

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 breast cancers (invasive and non-invasive), 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 EORTCQLQ-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 exposure to Olaparib (in plasma) in patients receiving Olaparib as adjuvant therapy

Conditions and MedDRA coding

Breast Cancer

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 18 years old and older
2. 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)
3. 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).
4. Completed adequate breast and axilla surgery.
5. 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.
6. ECOG 0-1.R50

Exclusion criteria 5

1. Any previous treatment with a PARP inhibitor, including olaparib and/or known hypersensitivity to any of the excipients of study treatment.
2. 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 ≥ 5years prior to randomisation and treated with no evidence of disease recurrence and for whom no more than one line of chemotherapy was applied.
3. 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 orphenobarbital and 3 weeks for other agents.
4. Whole blood transfusions in the last 120 days prior to entry to the study which may interfere with gBRCA testing
5. Evidence of metastatic breast cancer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Invasive Disease Free Survival (IDFS)

Secondary endpoints 7

1. Overall survival (OS)
2. Distant Disease Free Survival (DDFS)
3. 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. Patient Reported Outcomes from FACIT Fatigue and EORTCQLQ-C30 QoL questionnaires
5. Determination of BRCA mutation status using current and future BRCA mutation assays (gene sequencing and large rearrangement analysis)
6. Exposure to olaparib (in plasma) in patients receiving olaparib as adjuvant therapy
7. Safety

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Global Clinical Lead

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

12 EU/EEA countries · 169 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications