Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Sep 2013 → ongoing

Decision date (initial)

2024-03-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-511142-39-00

EudraCT number

2013-001551-13

ClinicalTrials.gov

NCT01844986

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the efficacy by progression free survival (PFS) investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.

Secondary objectives 5

1. To determine the efficacy of olaparib maintenance monotherapy compared to placebo patients by assessment of: a) overall survival b) time to earliest progression by RECIST or Cancer Antigen-125 or death c) time from randomization up to second progression
2. Compare effects of olaparib maintenance monotherapy with placebo on HRQoL assessed by the TOI of the FACT-O.
3. Assess 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 potential future BRCA mutation assays
4. To determine the efficacy of olaparib maintenance monotherapy compared to placebo patients by assessment of time from randomisation to: a) first subsequent therapy b) second subsequent therapy c) study treatment discontinuation or death
5. To assess the safety and tolerability of olaparib maintenance monotherapy.

Conditions and MedDRA coding

BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products, Food And Drug Administration, Swedish Medical Products Agency, Medicines Evaluation Board

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 4

1. PRINCIPAL INCLUSION CRITERIA (most important listed). Female patients with newly diagnosed, histologically confirmed, high risk advanced (FIGO stage III – IV) BRCA mutated high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer and / or fallopian-tube cancer who have completed first line platinum based chemotherapy (intravenous or intraperitoneal).
2. Stage III patients must have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery.
3. 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).
4. Patients who have completed first line platinum (eg. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation: • Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study.

Exclusion criteria 7

1. PRINCIPAL EXCLUSION CRITERIA (the most important are listed). BRCA1 and/or BRCA2 mutations that are considered to be non detrimental (e.g. "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favour polymorphism" or "benign polymorphism" etc).
2. Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC)
3. Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment.
4. Patients where more than one debulking surgery has been performed before randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and interval debulking surgery are eligible).
5. Patients who have previously been diagnosed and treated for earlier stage ovarian, fallopian tube or primary peritoneal cancer.
6. Patients who have previously received chemotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease).
7. Patients with synchronous primary endometrial cancer unless both of the following criteria are met: 1) stage <2 2) less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS) by investigator review of RECIST data

Secondary endpoints 7

1. Efficacy in patients following First Line Platinum Based Chemotherapy by assessment of: a) overall survival b) time to earliest progression by RECIST or Cancer Antigen-125 (CA- 125) c) time from randomisation to second progression.
2. The Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian Cancer (FACT-O) will be used to determine: a) Change from baseline in TOI score b) Proportion improved
3. Development and delivery of a BRCA mutation companion diagnostic
4. Adverse events, physical examination, vital signs including blood pressure, pulse, electrocardiogram and laboratory findings including clinical chemistry and haematology
5. Efficacy of olaparib by time to first subsequent therapy or death (TFST).
6. Efficacy of olaparib by time to second subsequent therapy or death (TSST).
7. Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT).

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

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

5 EU/EEA countries · 23 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 33 files

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

Application history

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