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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02477644
Other study ID # GINECO-OV125b
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date May 6, 2015
Est. completion date March 22, 2022

Study information

Verified date August 2022
Source Arcagy Research
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in Patients with Advanced FIGO Stage IIIB - IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and Bevacizumab Concurrent with Chemotherapy and in Maintenance.


Description:

Patients with advanced FIGO stage IIIB - IV high grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment, combining platinum-taxane chemotherapy and bevacizumab concurrent with chemotherapy and in maintenance.


Recruitment information / eligibility

Status Completed
Enrollment 806
Est. completion date March 22, 2022
Est. primary completion date March 22, 2019
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria: I-1. Female Patient must be =18 years of age. I-2. Signed informed consent and ability to comply with treatment and follow-up. I-3. Patient with newly diagnosed I-3-1 Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer, I-3-2 Histologically confirmed (based on local histopathological findings): - high grade serous or - high grade endometrioid or - other epithelial non mucinous ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation I-3-3 at an advanced stage: FIGO stage IIIB, IIIC, or IV of the 1988 FIGO classification. I-4. Patient who has completed prior to randomization first line platinum-taxane chemotherapy: 1. Platinum-taxane based regimen must have consisted of a minimum of 6 treatment cycles and a maximum of 9. However if platinum based therapy must be discontinued early as a result of non hematological toxicity specifically related to the platinum regimen, (i.e. neurotoxicity, hypersensitivity etc.), patient must have received a minimum of 4 cycles of the platinum regimen. 2. Intravenous, intraperitoneal, or neoadjuvant platinum based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle. Interval debulking is allowed. I-5. Patient must have received prior to randomization a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to realize only 2 cycles of bevacizumab in combination with the last 3 cycles of platinium-based chemotherapy. Bevacizumab treatment should be administered at a dose 15mg/kg q3 weeks up to a total of 15 months. I-6. Patient must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) from her first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout her first line treatment and prior to study randomization. I-7. Patient must be randomized at least 3 weeks and no more than 9 weeks after her last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from the previous chemotherapy must have resolved to CTC AE grade 1 or better (except alopecia and peripheral neuropathy). I-8. Patient must have normal organ and bone marrow function: 1. Hemoglobin = 10.0 g/dL. 2. Absolute neutrophil count (ANC) = 1.5 x 109/L. 3. Platelet count = 100 x 109/L. 4. Total bilirubin = 1.5 x institutional upper limit of normal (ULN). 5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x ULN, unless liver metastases are present in which case they must be = 5 x ULN. 6. Serum creatinine = 1.25 x institutional ULN and creatinine clearance > 50 mL/min. 7. Patient not receiving anticoagulant medication who has an International Normalized Ratio (INR) =1.5 and an Activated ProThrombin Time (aPTT) =1.5 x ULN. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or APTT is within therapeutic limits (according to site medical standard). If the patient is on oral anticoagulants, dose has to be stable for at least two weeks at the time of randomization. 8. Urine dipstick for proteinuria < 2+. If urine dipstick i s =2+, 24-hour urine must demonstrate <1 g of protein in 24 hours. 9. Normal blood pressure or adequately treated and controlled hypertension (systolic BP = 140 mmHg and/or diastolic BP = 90 mmHg). I-9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. I-10. Formalin fixed, paraffin embedded (FFPE) tumor sample from the primary cancer must be available for central BRCA testing and test result must be available for stratification. I-11. Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. (see appendix 4) I-12. For France only: In France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category. Exclusion Criteria: E-1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors). E-2. Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma. E-3. Patient with synchronous primary endometrial cancer unless both of the following criteria are met: 1. stage < II, 2. Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade III endometrioid adenocarcinoma OR = 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1 or 2 endometrioid adenocarcinoma. Patient with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium is not eligible. E-4. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS). Patient with a history of localized malignancy diagnosed over 5 years ago may be eligible provided she completed her adjuvant systemic therapy prior to randomization and that the patient remains free of recurrent or metastatic disease. Patient with history of primary triple negative breast cancer may be eligible provided she completed her definitive anticancer treatment more than 3 years ago and she remains breast cancer disease free prior to start of study treatment. E-5. Patient with myelodysplastic syndrome/acute myeloid leukemia history E-6. Patient having experienced for at least one cycle, a delay > 2 weeks due to prolonged hematological recovery during the first line chemotherapy E-7. Patient receiving radiotherapy within 6 weeks prior to study treatment E-8. Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery E-9. Previous allergenic bone marrow transplant. E-10. Any previous treatment with PARP inhibitor, including olaparib. E-11. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics). E-12. Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day. E-13. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir. E-14. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy. E-15. Clinically significant (e.g. active) cardiovascular disease, including: 1. Myocardial infarction or unstable angina within = 6 months of randomization, 2. New York Heart Association (NYHA) = grade 2congestive heart failure (CHF). 3. Poorly controlled cardiac arrhythmia despite medication (patient with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG, 4. Peripheral vascular disease grade = 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision). E-16. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to randomization. E-17. History or evidence of hemorrhagic disorders within 6 months prior to randomization. E-18. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation). E-19. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression. E-20. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures). E-21. Significant traumatic injury during 4 weeks prior to randomization. E-22. Non-healing wound, active ulcer or bone fracture. Patient with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection is eligible but require 3 weekly wound examinations. E-23. History of VEGF therapy related abdominal fistula or gastrointestinal perforation or active gastrointestinal bleeding within 6 months prior to the first study treatment. E-24. Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease. E-25. Patient with evidence of abdominal free air not explained by paracentesis or recent surgical procedure. E-26. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications. E-27. Pregnant or lactating women. E-28. Participation in another clinical study with an investigational product during her chemotherapy course immediately prior to randomization. E-29. Patient unable to swallow orally administered medication and patient with gastrointestinal disorders likely to interfere with absorption of the study medication. E-30. Patient with a known hypersensitivity to olaparib or any of the recipients of the product. E-31. Immunocompromised patient, e.g., with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids or patient who is known to be serologically positive for human immunodeficiency virus (HIV).

Study Design


Intervention

Drug:
Olaparib
Tablets, per os, 300 mg twice daily;
Placebo
Tablets, per os, 300 mg twice daily.

Locations

Country Name City State
Austria KH der Barmherzigen Brüder Graz Graz
Austria Medical University of Graz Graz
Austria Medical University of Innsbruck Innsbruck
Austria Landeskrankenhaus Salzburg Salzburg
Austria Krankenhaus Hietzing Vienna
Austria Medical University of Vienna Vienna
Belgium Institut Jules Bordet Bruxelles
Belgium Antwerp University Hospital Edegem
Belgium UZ Gasthuisberg Leuven
Belgium Hôpital de la Citadelle Liège
Belgium Clinique et maternité Sainte Elisabeth Namur
Belgium CHU Dinant Godinne Yvoir
Denmark Rigshospitalet Copenhagen
Denmark Herlev Hospital Herlev
Finland Kuopio University Hospital Kuopio
Finland Oulu University Hospital Oulu
Finland Tampere University Hospital Tampere
Finland Turku University Hospital Turku
France ICO Paul Papin Angers
France Institut Sainte-Catherine Avignon
France Hôpital Jean Minjoz Besancon
France Institut Bergonié Bordeaux
France Polyclinique Bordeaux Nord Bordeaux
France Centre François Baclesse Caen
France Centre Jean Perrin Clermont-ferrand
France Centre Georges François Leclerc Dijon
France Groupe Hospitalier Mutualiste de Grenoble Grenoble
France Centre Hospitalier Départemental Les Oudairies La Roche-sur-yon
France Hôpital Michallon - Centre Hospitalier Universitaire de Grenoble La Tronche
France Centre Jean Bernard - Clinique Victor Hugo Le Mans
France Centre Hospitalier Régional Universitaire de Lille - Hôpital Huriez Lille
France Centre Oscar Lambret Lille
France Centre Léon Bérard Lyon
France Institut Paoli Calmettes Marseille
France Hôpital de Mont-de-Marsan Mont-de-marsan
France ICM Val d'Aurelle Montpellier
France Centre Azuréen de Cancérologie Mougins
France Centre Catherine de Sienne - Group confluent Nantes
France Centre Antoine Lacassagne Nice
France Centre Hospitalier Régional d'Orléans Orleans
France Groupe Hospitalier Saint-Joseph Paris
France Hôpital Cochin Paris
France Hôpital des Diaconesses Paris
France Hôpital Européen Georges Pompidou Paris Ilhe De France
France Hopital Tenon Paris
France Institut Curie - Hopital Claudius Régaud Paris
France Clinique Francheville Perigueux
France Centre Hospitalier Lyon Sud Pierre-benite
France Centre CARIO - HPCA Plérin
France Hôpital de la Milétrie - CHU de Poitiers - Pôle Régional de Cancérologie Poitiers
France Centre Eugène Marquis Rennes
France Centre Henri Becquerel Rouen
France Hôpital René Huguenin, Institut Curie Saint-cloud
France ICO Centre René Gauducheau Saint-herblain
France Centre de Radiothérapie - Clinique Sainte-Anne Strasbourg
France Centre Paul Strauss Strasbourg
France Hôpitaux Universitaires de Strasbourg Strasbourg
France Clinique Pasteur - ONCOSUD Toulouse
France Institut Claudius Regaud Toulouse
France ICL Institut de Cancérologie de Lorraine Vandoeuvre-les-nancy
France Institut Gustave Roussy Villejuif
Germany Klinikum Aschaffenburg Aschaffenburg
Germany Klinikum Augsburg Augsburg
Germany Hochtaunus-Kliniken Bad Homburg
Germany Charité - Universitätsmedizin Berlin (CVK) Berlin
Germany HELIOS Klinikum Berlin-Buch Berlin
Germany Praxisklinik Krebsheilkunde für Frauen Berlin
Germany Onkologie Bottrop Bottrop
Germany GYNAEKOLOGICUM Bremen Bremen
Germany Städtisches Klinikum Dessau Dessau
Germany Universitätsklinikum Carl Gustav Carus Dresden
Germany Evangelisches Krankenhaus Düsseldorf Düsseldorf
Germany Universitätsklinikum Düsseldorf Düsseldorf
Germany Universitätsfrauenklinik Erlangen Erlangen
Germany Kliniken Essen Mitte Essen
Germany Universitätsklinikum Essen Essen
Germany Klinikum Esslingen Esslingen
Germany Klinikum der Johann Wolfgang Goethe-Universität Frankfurt
Germany Klinikum Frankfurt Höchst Frankfurt
Germany Universitätsfrauenklinik Freiburg Freiburg
Germany Universitäts-Frauenklinik Göttingen Göttingen
Germany Universitätsmedizin Greifswald Greifswald
Germany Klinkum Gütersloh Gütersloh
Germany Universitätsklinikum Halle Halle
Germany Albertinen Krankenhaus Hamburg
Germany Universitätsklinikum Hamburg-Eppendorf Hamburg
Germany Gynäkologisch-Onkologische Praxis Hannover Hannover
Germany Medizinische Hochschule Hannover Hannover
Germany Universitätsklinikum Heidelberg Heidelberg
Germany Universitätsklinikum Jena Jena
Germany St. Vincentius Kliniken Karlsruhe
Germany Klinikum Kassel Kassel
Germany Universitätsklinikum Schleswig-Holstein Kiel
Germany St. Elisabeth Krankenhaus Köln
Germany Universitätsfrauenklinik Köln Köln
Germany Klinikum Konstanz Konstanz
Germany HELIOS Klinikum Krefeld Krefeld
Germany Universitätsklinikum Schleswig-Holstein Lübeck
Germany Klinikum Ludwigsburg Ludwigsburg
Germany Universitätsklinikum Gießen und Marburg Marburg
Germany Johannes Wesling Klinikum Minden
Germany Klinikum der Universität München München
Germany Klinikum rechts der Isar München
Germany Universitätsklinikum Münster Münster
Germany Kliniken des Landkreises Neumarkt Neumarkt
Germany Sana Klinikum Offenbach Offenbach
Germany Ortenau Klinikum Offenburg
Germany Onkologie Ravensburg Ravensburg
Germany Universitätsfrauenklinik Regensburg Regensburg
Germany Klinikum am Steinenberg Reutlingen
Germany ROMed Klinikum Rosenheim Rosenheim
Germany Klinikum Südstadt Rostock
Germany Robert-Bosch-Krankenhaus Stuttgart
Germany Universitäts-Frauenklinik Tübingen Tübingen
Germany Universitätsklinikum Ulm Ulm
Germany HELIOS Dr. Horst Schmidt Kliniken Wiesbaden
Germany Marien Hospital Witten Witten
Germany amO Wolfsburg Wolfsburg
Germany Klinikum Worms Worms
Germany Universitätsklinikum Würzburg Würzburg
Italy Centro Riferimento Oncologico Aviano
Italy Policlinico S.Orsola-Malpighi Bologna
Italy Spedali Civili-Università di Brescia Brescia
Italy Ospedale Senatore Antonio Perrino Brindisi
Italy EO Ospedali Galliera Genova
Italy Ospedale San Luca Lucca
Italy Istituto Europeo di Oncologia Milano
Italy Istituto Nazionale Tumori Milano
Italy Istituto Nazionale Tumori - IRCCS Pascale Napoli
Italy Istituto Oncologico Veneto Padova
Italy Ospedale Santa Maria della Misericordia Perugia
Italy Ospedale Santa Chiara Pisa
Italy AO ASL 4 - Ospedale di Prato Prato
Italy Arcispedale S. M. Nuova Reggio Emilia
Italy Istituto Regina Elena Roma
Italy Policlinico Umberto I La Sapienza Roma
Italy Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore Roma
Italy Ospedale Mauriziano Torino
Italy Ospedale S. Anna Torino
Italy Ospedale Santa Chiara Trento
Japan Ehime University Hospital Ehime
Japan Hyogo Cancer Center Hyogo
Japan University of Tsukuba Hospital Ibaraki
Japan Kagoshima University Medical And Dental Hospital Kagoshima
Japan Saitama Medical University International Medical Center Saitama
Japan Jichi Medical University Hospital Tochigi
Japan National Cancer Center Hospital Tokyo
Monaco Centre Hospitalier Princesse Grace Monaco
Spain H. U. Fundación Alcorcón Alcorcón
Spain C.S. Parc Taulí Barcelona
Spain H. de la Santa Creu i Sant Pau Barcelona
Spain H. U. Reina Sofía Córdoba
Spain H.U. Arnau de Vilanova Lleida
Spain H. U. 12 de Octubre Madrid
Spain H. U. Ramón y Cajal Madrid
Spain MD Anderson Cancer Center Madrid Madrid
Spain H.U. Central de Asturias Oviedo
Spain Complejo Hospitalario de Navarra Pamplona
Spain H. General Universitario de Valencia Valencia
Spain H. U. P. La Fe Valencia
Spain Instituto Valenciano de Oncología València
Spain H. U. Miguel Servet Zaragoza
Sweden Linköping University Hospital Linköping

Sponsors (9)

Lead Sponsor Collaborator
Arcagy Research Arbeitsgemeinschaft Gynaekologische Onkologie Austria, Arbeitsgemeinschaft Gynaekologishe Onkologie Germany, Belgian Gynaecological Oncology Group, Grupo Español de Investigación en Cáncer de Ovario, Gynecologic Oncology Trial & Investigation Consortium, Mario Negri Gynecologic Oncology group (MaNGO), Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies, Nordic Society of Gynaecological Oncology - Clinical Trials Unit

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  Finland,  France,  Germany,  Italy,  Japan,  Monaco,  Spain,  Sweden, 

References & Publications (1)

Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Efficacy by progression free survival (PFS1) phase up to a total of 15 months
Secondary Overall survival Overall survival is defined as the time from the date of randomization until death due to any cause. Study end
Secondary Time to earliest progression by RECIST or CA-125 Time to earliest progression by RECIST v. 1.1 or CA-125 or death is defined as the time from randomization to the earliest date of RECIST or CA-125 progression or death by any cause. Study end
Secondary Second Progression Free Survival (PFS2) Time from randomization to second progression is defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the primary variable PFS, or date of death. Study end
Secondary Time to start of first subsequent therapy or death (TFST) Time to start of first subsequent therapy or death (TFST) will be assessed. TFST is defined as the time from the date of randomization to the earliest of the date of anti-cancer therapy start date following study treatment discontinuation, or death. Study end
Secondary Time to start of second subsequent therapy or death (TSST) Time to start of second subsequent therapy or death (TSST) will be assessed. TSST is defined as the time from the date of randomization to the earliest of the date of second subsequent anti-cancer therapy start date following study treatment discontinuation, or death. Study end
Secondary Safety and Tolerability Study end
Secondary Patient reported outcome 2 years after last patient included
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