Clinical trial NCT03106987: A Study to Examine Olaparib Maintenance Retreatment in Patients With Epithelial Ovarian Cancer.
Official title: A Phase IIIb, Randomised, Double-blind, Placebo-controlled, Multicentre Study of Olaparib Maintenance Retreatment in Patients With Epithelial Ovarian Cancer Previously Treated With a PARPi and Responding to Repeat Platinum Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epithelial Ovarian Cancer
Keywords: polymerisation inhibitor (PARPi)
PARPi re-treatment
BRCA1/2 (+ve)
BRCA1/2 (-ve)
Olaparib
ovarian cancer
progression free survival (PFS)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
First posted: 2017-04-11
Enrollment: 220
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The OReO study will be a Phase IIIb, randomised, double-blind, placebo-controlled, multicentre study to assess the efficacy and tolerability of Olaparib retreatment, versus matching placebo, in non-mucinous epithelial ovarian cancer (EOC) patients (including patients with primary peritoneal and/or fallopian tube cancer)

Detailed description: The OReO study will investigate the efficacy and safety of Olaparib maintenance re-treatment in patients with relapsed non-mucinous EOC, who have had disease progression following maintenance therapy with a Polyadenosine 5'diphosphoribose \[poly (ADP ribose)\] polymerisation inhibitor (PARPi) and a complete or partial radiological response to subsequent treatment with platinum-based chemotherapy or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125. Patients will be enrolled on the basis of their breast cancer susceptibility gene (BRCA1, BRCA2) status into one of two cohorts (BRCA1/2 \[+ve\] and BRCA1/2 \[-ve\]). The BRCA1/2 (+ve) and BRCA1/2 (-ve) cohorts will be randomised separately. Within each cohort, patients will be randomised by prospective allocation in a 2:1 ratio (Olaparib: matching placebo).

Eligibility criteria: Inclusion criteria

* Provision of informed consent prior to any study specific procedures
* Female patients ≥18 years of age, with histologically diagnosed relapsed non-mucinous epithelial ovarian cancer (EOC) (including primary peritoneal and/or fallopian tube cancer) (Non-mucinous EOC includes patients with serous, endometrioid, and transitional cell tumours, and those with mixed histology where one of these subtypes is predominant (\>50%). Inclusion of other subtypes should first be discussed with the Medical Monitor).
* Documented BRCA1/2 status.
* Patients must have received one prior PARPi therapy PARPi therapy includes any agent (including Olaparib) used in a maintenance setting For the BRCA1/2 (+ve) cohort, the duration of first PARPi exposure must have been ≥18 months following a first line of chemotherapy or ≥12 months following a second or subsequent line of chemotherapy For the BRCA1/2 (-ve) cohort, the duration of first PARPi exposure must have been ≥12 months following a first line of chemotherapy or ≥6 months following a second or subsequent line of chemotherapy For the last chemotherapy course immediately prior to randomisation on the study Patients must have received a platinum-based chemotherapy regimen (carboplatin, cisplatin or oxaliplatin) and have received at least 4 cycles of treatment Patients must be, in the opinion of the investigator, in response (partial or complete radiological response) or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy) and no evidence of a rising CA-125, as defined below, following completion of this chemotherapy course Pre-treatment CA-125 measurements must meet criterion specified below
* If the first value is within upper limit of normal (ULN) the patient is eligible to be randomised and a second sample is not required
* If the first value is greater than ULN a second assessment must be performed at least 7 days after the first. If the second assessment is ≥ 15% more than the first the patient is not eligible.

Patients must not have received bevacizumab during this course of treatment. Bevacizumab use as part of an earlier line of chemotherapy is permitted Patients must not have received any investigational agent during this course of treatment Patients must be randomised within 8 weeks of their last dose of chemotherapy (last dose is the day of the last infusion)

* Patients must have normal organ and bone marrow function measured within 28 days of randomization.
* Eastern Cooperative Oncology Group performance status 0-1
* Patients must have a life expectancy ≥16 weeks.
* Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment. or No measurable disease following a complete response to most recent chemotherapy (+/- surgery)
* A formalin fixed, paraffin embedded (FFPE) tumour sample from the cancer of sufficient quantity and quality (as specified in the Covance Central Laboratory Services Manual) must be available for future central testing of tumour genetic status.
* For inclusion in the optional biomarker research, patients must sign an informed consent for biomarker research.

Exclusion criteria:

* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
* Participation in another clinical study with an investigational product during the chemotherapy course immediately prior to randomisation.
* Other malignancy within the last 5 years except the ones detailed in the exclusion criteria section of study protocol.
* Resting electrocardiogram (ECG) with corrected QT interval (QTc) \>470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome6. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative radiotherapy) within 3 weeks prior to study treatment.
* Concomitant use of known strong cytochrome P450 (CYP) subfamily 3A (CYP3A) inhibitors or moderate CYP3A inhibitors.
* Concomitant use of known strong or moderate CYP3A inducers.
* Persistent toxicities (Common Terminology Criteria for Adverse Event \[CTCAE\] grade 2 or higher) caused by previous cancer therapy, excluding alopecia and stable Grade 2 peripheral neuropathy .
* Patients with current or previous myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
* Patients with symptomatic uncontrolled brain metastases.
* Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
* Patients with a known hypersensitivity to Olaparib or any of the excipients of the product.
* Patients with a known active hepatitis (i.e..Hepatitis B or C).
* Patient who have received a whole blood transfusion within 30 days prior to screening tests (packed red blood cells and platelet transfusions are acceptable).

Primary outcomes:
measure: Efficacy: Progression-free Survival (PFS)
timeFrame: At randomization visit and at every 12 weeks (+/- 7 days) until objective radiological disease progression as determined by the investigator or other discontinuation criteria are met (assessed upto 3.8 years)
Secondary outcomes:
measure: Efficacy: Overall Survival (OS)
timeFrame: From randomisation till Long-term follow-up (12-weekly beyond 30 days after last dose of study treatment) assessed upto 3.8 years
measure: Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria
timeFrame: At screening (Visit 1) and at every 12 weeks (±7 days), until objective disease progression, based on progressive serial elevation of serum CA-125 according to the GCIG criteria, or until discontinuation for other reasons (assessed upto 3.8 years)
measure: Efficacy: Time to First Subsequent Treatment Commencement (TFST)
timeFrame: From follow-up i.e. 30 days after last dose of study medication till end of study (assessed every 12 weeks upto 3.8 years)
measure: Efficacy: Time to Second Subsequent Treatment Commencement (TSST)
timeFrame: From follow-up i.e. 30 days after last dose of study medication till end of study (assessed every 12 weeks upto 3.8 years)
measure: Efficacy: Time to Study Treatment Discontinuation (TDT)
timeFrame: From follow-up 30 days after last dose of study medication till long-term follow-up i.e. 12-weekly beyond 30 days after last dose of study treatment
measure: Efficacy: Change From Baseline in Health-related Quality of Life (HRQoL)
timeFrame: At Baseline, and from Day 1 until objective disease progression (assessed upto 2 years)
measure: Number of Patients With Adverse Events (AEs), and Serious Adverse Events (SAEs)
timeFrame: At Baseline and from Day 1 till follow-up i.e. 30 days after last dose of study medication (assessed upto 3.8 years)
measure: Number of Patients With Adverse Event of Special Interest (AESI).
timeFrame: At Baseline and from Day 1 till long-term follow-up i.e. 12-weekly beyond 30 days after last dose of study treatment (assessed upto 3.8 years)
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: London
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: København Ø
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Besançon
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Caen Cedex 05
country: France
facility: Research Site
city: Clermont Ferrand cedex 01
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Paris Cedex 20
country: France
facility: Research Site
city: Paris Cedex 5
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Pierre Benite
country: France
facility: Research Site
city: Plerin SUR MER
country: France
facility: Research Site
city: Saint Herblain
country: France
facility: Research Site
city: Saint-cloud
country: France
facility: Research Site
city: Toulouse Cedex 09
country: France
facility: Research Site
city: Vandoeuvre-Les-Nancy
country: France
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: petach Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Candiolo
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Lecce
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Grzepnica
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Hôpital Hôtel-Dieu
name: Eric Pujade-Lauraine, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: