A Clinical Trial to Confirm the Efficacy of Olaparib in Combination with Bevacizumab, Administered as Maintenance Therapy After a Frontline Platinum Based Chemotherapy Plus Bevacizumab, in the Treatment of Patients with Ovarian Tumours Showing a Genetic Defects in a DNA Repair Mechanism Called Homologous Recombination (Defined as Hrd Positive, Where Hrd Means Homologous Recombination Deficiency)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mario Negri Institute For Pharmacological Research

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Jun 2023 → ongoing

Decision date (initial)

2023-06-16

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Astrazeneca

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

- define the proportion of patients with advanced high grade epithelial ovarian cancer (EOC) HRD-positive who will be treated at first line with olaparib in combination with bevacizumab as maintenance
and to describe their clinical and demographic characteristics.
- confirm, in a setting close to clinical practice, the efficacy of olaparib concomitant with bevacizumab as maintenance treatment after first-line chemotherapy in patients with advanced high grade EOC
HRD-positive and who have received bevacizumab in combination with chemotherapy.

Secondary objectives 1

1. 1) to describe the compliance to olaparib administered with bevacizumab in terms of treatment modifications and duration of treatment; 2) to describe the safety profile of olaparib added to bevacizumab; and 3) to describe its efficacy in terms of PFS2 (defined as the time from starting olaparib to the second progression or death whichever comes first) and overall survival (OS).

Conditions and MedDRA coding

Patients with a confirmation of advanced, high grade epithelial ovarian, fallopian tube or primary peritoneal cancer at surgery or at diagnostic biopsy and fulfilling the eligibility criteria to start a chemotherapy regimen in association with bevacizumab. Tumor samples at surgery will be retrieved and evaluated for the HRD status by Myriad Mychoice CDxPlus test. After surgery patients will start a standard platinum-based chemotherapy plus bevacizumb. Patients who will be in complete or partial response after frontline platinum-based chemotherapy plus bevacizumab and with HRD-positive tumor according to the Myriad Mychoice CDx Plus evaluation (including BRCA1-2 mutated tumors) and fulfilling specific eligibility criteria, will start to take olaparib in addition to bevacizumab as maintenance therapy.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.Provision of informed consent. 2. Subject must be ≥ 18 years of age inclusive, at the time of signing the informed consent form. 3.Patient with newly diagnosed high-grade epithelial ovarian, primary peritoneal and/or fallopian-tube cancer 4.Patients with advanced disease (FIGO stage III-IV). 5.Formalin-fixed, paraffin-embedded (FFPE) tumour samples from primary cancer must be available for the central testing of HRD status (Myriad Mychoice CDx Plus). If there is not written confirmation of the availability of an archived tumour sample before enrolment, the patient will not be eligible for the study. 6.Patients suitable to receive a platinum-taxane chemotherapy plus bevacizumab. 7. Patients must have normal organ and bone marrow function values measured before administration of platinum-based chemotherapy plus bevacizumab 8. Normal blood pressure (BP) or adequately treated and controlled hypertension (systolic BP ≤ 140 mmHg and/or diastolic BP ≤ 90 mmHg 9.Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 10.Patients must have a life expectancy ≥ 16 weeks.

Exclusion criteria 1

1. 1.Any previous treatment with PARP inhibitor, including Olaparib. 2.Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. 3.Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. 4.Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. 5.Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 6.Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). 7. Patients with known active hepatitis (i.e. Hepatitis B or C). 8.Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). 9.Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures (including sample collection), restrictions and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The efficacy will be evaluated in terms of PFS rate at 24 months. PFS will be defined as the time from the start of olaparib therapy until disease progression or death whichever comes first

Secondary endpoints 1

1. Compliance in terms of treatment modifications and the duration of treatment with olaparib. The safety profile of olaparib in terms of: maximum toxicity grade experienced by each patient, for each toxicity; grade 3-4 toxicity for each type of toxicity; type, frequency, and nature of SAEs, SADR, SUSAR. Efficacy in terms of PFS2, which is defined as the time from starting olaparib to the second progression or death whichever comes first.

Investigational products

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

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mario Negri Institute For Pharmacological Research

Sponsor organisation

Mario Negri Institute For Pharmacological Research

Address

Via Giuseppe La Masa 19

City

Milan

Postcode

20156

Country

Italy

Scientific contact point

Organisation

Mario Negri Institute For Pharmacological Research

Contact name

Elena Biagioli

Public contact point

Organisation

Mario Negri Institute For Pharmacological Research

Contact name

Elena Biagioli

Locations

1 EU/EEA country · 11 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 8 files

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

Application history

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