WoO: Window of Opportunity Trial of Olaparib and Durvalumab in Histologically Proven EOC

NCT04644289 | Recruiting Phase 2

• 3 other identifiers: AGO-OVAR 272020-005101-122024-511780-28-00
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, prospective, open-label, phase II trial. Patients with suspected advanced ovarian cancer planned to undergo diagnostic laparoscopy for histologic confirmation and evaluation of disease spread will be registered into the trial after providing a 1st written informed consent.

Conditions

Epithelial Ovarian Cancer

Keywords

Epithelial Ovarian Cancer; Olaparib; Durvalumab

Outcome Measures

Primary Outcomes (1)

• Feasibility of the WoO procedure for olaparib alone (cohort a) & olaparib in combination with durvalumab (cohort b)

  Defined as the successful completion of the WoO therapy: * Relative dose intensity (RDI) of ≥80% * No treatment-related surgical delays * Adherence to therapeutic strategy * Lack of clinical progression prior to primary debulking surgery * No treatment-related toxicities of any grade that in the judgment of the investigator or surgeon significantly interfered with the subject's optimal perioperative management

  Between registration into the trial until 60 days after surgery or 60 days after the originally planned surgery date in case of switch of therapeutic strategy.

Secondary Outcomes (3)

• Safety of the WoO procedure

  Between registration into the trial until 60 days after surgery or 60 days after the originally planned surgery date in case of switch of therapeutic strategy.

• Proportion of circulating tumor DNA (ctDNA) Mutation positive patients

  At baseline

• CDR21

  At day 21

Other Outcomes (2)

• Progression free survival (PFS)

  From registration until progression or death or date of LPLV whichever occurs first. Depending on the time point of inclusion into the trial the expected maximum follow-up time for an individual patient might range between 2.5 and 4,6 years.

• PD-L1 expression

  At day 21

Study Arms (2)

cohort A - olaparib monotherapy

OTHER

Olaparib tablets 2 × 300mg per day for 3 weeks (max. 28 days) prior to surgery until one day prior to surgery or withdrawal of informed consent. Patients will receive the indicated standard of care (SoC) chemotherapy plus or minus Bevacizumab as per investigators discretion, followed by SoC maintenance treatment according to the national S3-guideline and treating physician's choice. They can be offered: For patients in cohort A who have received all possible licensed treatment regimens according to the national guideline or for whom further licensed treatment options are not available or contraindicated, Olaparib may be offered as investigational maintenance therapy for up to 24 months.

Drug: olaparib

cohort B - olaparib + durvalumab combination

OTHER

Olaparib tablets 2 × 300mg per day for 3 weeks (max. 28 days) plus Durvalumab 1500mg iv as a single dose prior to surgery (corresponding to 1 single cycle). Patients will receive the indicated standard of care (SoC) chemotherapy plus or minus Bevacizumab as per investigators discretion, followed by SoC maintenance treatment according to the national S3-guideline and treating physician's choice. They can be offered: Patients in cohort B may be offered Durvalumab 1120mg iv Q3W during chemotherapy treatment phase in combination with bevacizumab (unless contraindicated) and as maintenance for a total of up to 24 months (1120mg Q3W) in combination with Bevacizumab (for a total of 15 months, unless contraindicated) and Olaparib for a total of 24 months. For HRD-positive patients Durvalumab will be an investigational agent; for HRD-negative patients Durvalumab and Olaparib will be investigational agents.

Drug: olaparib; Drug: durvalumab

Interventions

olaparib DRUG

Olaparib tablets are administrated orally 300 mg twice daily.

Also known as: Lynparza

cohort A - olaparib monotherapy; cohort B - olaparib + durvalumab combination

durvalumab DRUG

Durvalumab is administered 1500mg iv as a single dose prior to surgery (corresponding to 1 single cycle) .

Also known as: Imfinzi

cohort B - olaparib + durvalumab combination

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• WoO pre-treatment (screening phase):
• Patients with presumed and previously untreated advanced stage ovarian cancer planned to undergo laparoscopy for histologic diagnosis and treatment planning
• Patients willing and able to comply with the study protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Patients able and willing to provide fresh frozen biopsy samples from laparoscopy as well as primary debulking for translational endpoints as well as serial liquid biopsies
• Patients able and willing to provide formaldehyde-fixed paraffin embedded (FFPE) tissue samples from laparoscopy and primary debulking surgery
• Patients aged ≥18 years
• Patients must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Provision of signed and dated, written ICF for the mandatory biomarker and genetic re-search as well as the clinical/therapeutic part of the study prior to any mandatory study specific procedures, sampling, and analyses
• Eastern cooperative oncology group (ECOG) performance status 0-1 (see Appendix 1)
• Patients must have a life expectancy ≥16 weeks
• Ability to take oral medication
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential (WOCBP): negative serum pregnancy test within 28 days of study treatment and confirmed neagtive urine or serum pregnancy test prior to treatment on day 1.
• Postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50

You may not qualify if:

• Medical conditions:
• Disease requiring urgent surgical intervention
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the study protocol
• Significant uncontrolled symptom burden (e.g. but not necessarily limited to large volume ascites, shortness of breath on exertion, pain requiring opioid medication, signs of (sub)ileus
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, recent (within 3 months) myocardial infarction, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease (optional criteria that is dependent on the patient population under investigation).
• Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, conges-tive heart failure, QTcF prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• a. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with olaparib, durvalumab or the combination may be included only after consultation with the coordinating investigator.
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).
• Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Evidence of central nervous system (CNS) or leptomeningeal metastases.
• 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.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders or any status that might interfere with resorption of the respective study drugs, e.g. parenteral nutrition, short bowel syndrome likely to interfere with absorption of the study medication.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).

Sponsors & Collaborators

• AGO Research GmbH: lead

Study Sites (6)

Universitätsklinikum Mannheim GmbH, Frauenklinik

Mannheim, Baden-Wurttemberg, 68167, Germany

RECRUITING

Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Frauenheilkunde

München, Bavaria, 81675, Germany

RECRUITING

Mammazentrum HH am Krankenhaus Jerusalem, Gynäkologisches Operationszentrum Hamburg

Hamburg, Hamburg, 20357, Germany

RECRUITING

KEM Essen | Evang. Kliniken Essen Mitte

Essen, North Rine-Westphalia, 45136, Germany

RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden an der technischen Universität Dresden, Gynäkologisches Krebszentrum und Regionales Brustzentrum Dresden am Universitäts-KrebsCentrum

Dresden, Saxony, 01307, Germany

RECRUITING

Charité Berlin, Klinik für Gynäkologie mit Zentrum für onkologische Chirurgie

Berlin, State of Berlin, 13353, Germany

RECRUITING

Related Links

• Homepage of AGO Study Group

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

olaparib; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Frederik Marmé, MD

  Universitätsklinikum Mannheim, Frauenklinik

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yvonne Treffner, Dr.

CONTACT

+49 201 959812-17; ytreffner@ago-ovar.de

Jana Warby

CONTACT

+49 201 959812-20; jwarby@ago-ovar.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be treated in two consecutive cohorts (A, B) of 15 to 30 (cohort A) and 30 (cohort B) patients each, with A) olaparib alone or B) olaparib in combination with durvalumab. Treatment allocation will take please in two consecutive cohorts rather than by randomization. This will allow to evaluate the safety and feasibility in a step-wise approach. A trial steering committee (TSC) meeting will take place between the cohorts to review safety and feasibility prior to starting the second cohort. The safety follow-up of the first cohort will take 90 days as of the first dose of therapy.

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: November 25, 2020
• Study Start: May 5, 2022
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: October 3, 2025

Record last verified: 2025-09

Locations

DE (6)