NCT03106987

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)

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
220

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jun 2017

Longer than P75 for phase_3

Geographic Reach
11 countries

82 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 24, 2017

Completed
18 days until next milestone

First Posted

Study publicly available on registry

April 11, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

June 8, 2017

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 15, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 17, 2022

Completed
2 months until next milestone

Results Posted

Study results publicly available

April 19, 2022

Completed
Last Updated

October 7, 2022

Status Verified

June 1, 2022

Enrollment Period

3.7 years

First QC Date

March 24, 2017

Results QC Date

February 15, 2022

Last Update Submit

September 13, 2022

Conditions

Keywords

polymerisation inhibitor (PARPi)PARPi re-treatmentBRCA1/2 (+ve)BRCA1/2 (-ve)Olaparibovarian cancerprogression free survival (PFS)

Outcome Measures

Primary Outcomes (1)

  • Efficacy: Progression-free Survival (PFS)

    PFS (per RECIST 1.1) was defined as the time from randomisation until the date of Investigator assessed objective radiological disease progression or death (by any cause in the absence of disease progression). Objective progression (per RECIST 1.1) is defined as at least a 20% increase in the sum of the diameters of the target lesions and an absolute increase of \>5 mm, or an overall non-target lesion assessment of progression or a new lesion. Patients who have not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.

    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 (8)

  • Efficacy: Overall Survival (OS)

    From randomisation till Long-term follow-up (12-weekly beyond 30 days after last dose of study treatment) assessed upto 3.8 years

  • Efficacy: Time to Progression by Gynecologic Cancer Intergroup (GCIG) Criteria

    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)

  • Efficacy: Time to First Subsequent Treatment Commencement (TFST)

    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)

  • Efficacy: Time to Second Subsequent Treatment Commencement (TSST)

    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)

  • Efficacy: Time to Study Treatment Discontinuation (TDT)

    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

  • +3 more secondary outcomes

Study Arms (2)

Active Comparator: Olaparib

EXPERIMENTAL

Olaparib 300mg tablets administered orally twice daily continuously.

Drug: Active Comparator: Olaparib tablets

Placebo Comparator: Placebo

PLACEBO COMPARATOR

Matching placebo 300mg tablets administered orally twice daily continuously.

Drug: Placebo

Interventions

Olaparib 300mg Olaparib tablets taken orally twice daily (except where this dose and formulation was previously not tolerated) until objective radiological disease progression as per RECIST 1.1 or as long as in the Investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.

Also known as: Olaparib tablets
Active Comparator: Olaparib

Placebo 300mg placebo tablets taken orally twice daily (except where this dose and formulation was previously not tolerated) until objective radiological disease progression as per RECIST 1.1 or as long as in the Investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria.

Placebo Comparator: Placebo

Eligibility Criteria

Age18 Years - 130 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of informed consent prior to any study specific procedures
  • 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.

You may not qualify if:

  • 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.
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (82)

Research Site

Leuven, 3000, Belgium

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Namur, 5000, Belgium

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London, Ontario, N6A 4L6, Canada

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Toronto, M5G 2M9, Canada

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Aalborg, 9000, Denmark

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København Ø, 2100, Denmark

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Odense C, 5000, Denmark

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Besançon, 25000, France

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Bordeaux, 33076, France

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Caen, 14076, France

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Clermont-Ferrand, 63011, France

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Lille, 59000, France

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Lyon, 69008, France

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Montpellier, 34298, France

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Nantes, 44202, France

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Nice, 6189, France

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Paris, 75012, France

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Paris, 75015, France

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Paris, 75020, France

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Paris, 75248, France

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Pierre-Bénite, 69495, France

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Plerin SUR MER, 22190, France

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Saint-Cloud, 92210, France

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Saint-Herblain, 44805, France

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Toulouse, 31059, France

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Vandœuvre-lès-Nancy, 54511, France

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Dresden, 01307, Germany

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Essen, 45136, Germany

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Frankfurt, 60596, Germany

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Hamburg, 20246, Germany

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Heidelberg, 69120, Germany

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Jena, 07747, Germany

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Lübeck, 23538, Germany

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Mannheim, 68167, Germany

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München, D-80336, Germany

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Rostock, 18057, Germany

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Stuttgart, 70376, Germany

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Ulm, 89075, Germany

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Wiesbaden, 65199, Germany

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Jerusalem, Israel

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Kfar Saba, 49281, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5265601, Israel

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Tel Aviv, 6423906, Israel

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Bologna, 40138, Italy

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Brescia, 25123, Italy

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Candiolo, 10060, Italy

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Catania, 95100, Italy

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Lecce, 73100, Italy

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Milan, 20132, Italy

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Milan, 20133, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Reggio Emilia, 42100, Italy

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Roma, 00168, Italy

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Torino, 10126, Italy

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Oslo, N-0379, Norway

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Grzepnica, 72-003, Poland

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Lublin, 20-090, Poland

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Olsztyn, 10-513, Poland

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Poznan, 60-569, Poland

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Warsaw, 02-781, Poland

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A Coruña, 15006, Spain

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Barcelona, 08036, Spain

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Córdoba, 14004, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 08035, Spain

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Madrid, 28033, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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Seville, 41013, Spain

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Valencia, 46009, Spain

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Valencia, 46010, Spain

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Valencia, 46026, Spain

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Glasgow, G12 OYN, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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London, SW36JJ, United Kingdom

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London, W12 0HS, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

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Sutton, SM25PT, United Kingdom

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Taunton, TA1 5DA, United Kingdom

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Related Publications (1)

  • Pujade-Lauraine E, Selle F, Scambia G, Asselain B, Marme F, Lindemann K, Colombo N, Madry R, Glasspool R, Vergote I, Korach J, Lheureux S, Dubot C, Oaknin A, Zamagni C, Heitz F, Gladieff L, Rubio-Perez MJ, Scollo P, Blakeley C, Shaw B, Ray-Coquard I, Redondo A; OReO/ENGOT-ov38 investigators. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023 Dec;34(12):1152-1164. doi: 10.1016/j.annonc.2023.09.3110. Epub 2023 Oct 4.

Related Links

MeSH Terms

Conditions

Carcinoma, Ovarian EpithelialOvarian Neoplasms

Interventions

olaparib

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Results Point of Contact

Title
Global Clinical Head
Organization
AstraZeneca Clinical Study Information Center

Study Officials

  • Eric Pujade-Lauraine, MD, PhD

    Hôpital Hôtel-Dieu

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2017

First Posted

April 11, 2017

Study Start

June 8, 2017

Primary Completion

February 15, 2021

Study Completion

February 17, 2022

Last Updated

October 7, 2022

Results First Posted

April 19, 2022

Record last verified: 2022-06

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
More information

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