Window-of-opportunity Proof-of-concept, Non-randomized, Open-label Phase II Trial of Olaparib Given Alone (Cohort A) or in Combination With Durvalumab (Cohort B) Prior to Primary Debulking Surgery in Histologically Proven High-grade Epithelial Ovarian Cancer (EOC)

Who is this study for? Patients with Epithelial Ovarian Cancer
What treatments are being studied? Olaparib
Status: Recruiting
Location: See all (6) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

‣ radiation-induced oophorectomy with last menses \>1 year ago

‣ chemotherapy-induced menopause with \>1 year interval since last menses

‣ surgical sterilisation (bilateral oophorectomy or hysterectomy)

⁃ Women of childbearing potential (WOCBP) and their partners, who are sexually active, must agree to the use of 2 highly effective forms of contraception in combination. This should be started from the signing of the informed consent and continue throughout the period of taking study treatment and for at least 6 months after last dose of study drug(s), or they must totally/truly abstain from any form of sexual intercourse.

⁃ WoO treatment phase:

⁃ Confirmed advanced (FIGO IIB/III/IV) high-grade, non-mucinous, non-clear cell epithelial ovarian, fallopian tube or primary peritoneal cancer or known (BReast CAncer) BRCA mutation and any histologic type

⁃ Planned primary debulking surgery after confirmation of diagnosis and disease evaluation during laparoscopy

⁃ Body weight \>30kg

⁃ Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

∙ Haemoglobin ≥10.0 g/dL with no blood transfusion in the past 28 days

‣ Absolute neutrophil count (ANC) ≥1.5×10\^9/L

‣ Platelet count ≥100×10\^9/L

‣ Total bilirubin ≤1.5 × institutional upper limit of normal (ULN)

‣ Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT) / alanine aminotransferase (ALT), serum glutamic pyruvate transaminase (SGPT) ≤2.5 × institutional upper limit of normal unless liver metastases are present in which case they must be ≤5×ULN. (cave: patients with intrahepatic metastases affecting liver function test might not be candidates for primary debulking surgery)

‣ Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test:

• Estimated creatinine clearance=((140-age \[years\])\*weight (kg))/(serum creatinine (mg/dL)\*72)(\* 0,85) 17. Patients must have successfully contributed blood and tissue samples as per requirements.

Locations
Other Locations
Germany
Charité Berlin, Klinik für Gynäkologie mit Zentrum für onkologische Chirurgie
RECRUITING
Berlin
Universitätsklinikum Carl Gustav Carus Dresden an der technischen Universität Dresden, Gynäkologisches Krebszentrum und Regionales Brustzentrum Dresden am Universitäts-KrebsCentrum
RECRUITING
Dresden
KEM Essen | Evang. Kliniken Essen Mitte
RECRUITING
Essen
Mammazentrum HH am Krankenhaus Jerusalem, Gynäkologisches Operationszentrum Hamburg
RECRUITING
Hamburg
Universitätsklinikum Mannheim GmbH, Frauenklinik
RECRUITING
Mannheim
Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Frauenheilkunde
RECRUITING
München
Contact Information
Primary
Yvonne Treffner, Dr.
ytreffner@ago-ovar.de
+49 201 959812-17
Backup
Jana Warby
jwarby@ago-ovar.de
+49 201 959812-20
Time Frame
Start Date: 2022-05-05
Estimated Completion Date: 2028-06
Participants
Target number of participants: 60
Treatments
Other: cohort A - olaparib monotherapy
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.
Other: cohort B - olaparib + durvalumab combination
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.
Related Therapeutic Areas
Sponsors
Leads: AGO Research GmbH

This content was sourced from clinicaltrials.gov