Clinical trial NCT01874353: Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
Official title: Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Platinum Sensitive
BRCA Mutated
Relapsed Ovarian Cancer
Following Complete or Partial Response to Platinum Based Chemotherapy
Keywords: BRCA
Ovarian cancer
Chemotherapy
PARP Inhibitor
Platinum sensitive
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: Myriad Genetic Laboratories, Inc.
name: Merck Sharp & Dohme LLC
First posted: 2013-06-11
Enrollment: 327
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: A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)) who have responded following platinum based chemotherapy.

Detailed description: Comparison of olaparib against a placebo in patients with ovarian cancer whose cancer has already improved by taking platinum based chemotherapy. The patients must also have a fault in their DNA which codes for the BRCA protein. The BRCA protein helps mend broken DNA in the cells of the body; if this protein doesn't work properly it can increase the chance of getting cancer. The aim of this study is to see whether patients taking olaparib tablets last longer until their cancer gets worse, compared to those taking the placebo tablet. The study is also looking to see if there is an overall improvement to how long the patients survive whilst taking olaparib tablets compared to the placebo tablets; and the quality of their life whilst living with ovarian cancer.

Eligibility criteria: Inclusion Criteria:

* Patients must be ≥ 18 years of age.

  * Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.
  * Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
  * Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation

For the penultimate chemotherapy course prior to enrolment on the study:

• Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy

For the last chemotherapy course immediately prior to randomisation on the study:

* 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, following completion of this chemotherapy course
* Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin) and have received at least 4 cycles of treatment
* Patients must be randomized within 8 weeks of their last dose of chemotherapy
* Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
* BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism" etc.)
* Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.

Primary outcomes:
measure: Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)
timeFrame: Radiologic scans performed at baseline then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression. Assessed until 19 Sep 2016 DCO (16 Jan 2017 DCO for China Cohort); up to a maximum of 36 months.
Secondary outcomes:
measure: Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival
timeFrame: Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.
measure: Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death
timeFrame: CA-125 at baseline then every 4 wks. Radiologic scans at baseline then every ~12 wks up to 72 wks, then every ~ 24 wks until objective radiological disease progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths.
measure: Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression
timeFrame: Scans at baseline then every 12 wks for 72 wks, then every 24 wks until first progression. Assessments then per local practice every 12 wks until second progression. Assessed until 19Sep2016 DCO (16Jan2017 DCO for China Cohort); up to a max of 36 mths
measure: Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)
timeFrame: Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months. Assessed until 19 Sep 2016 DCO.
measure: Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST)
timeFrame: Time elapsed from randomization to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.
measure: Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST)
timeFrame: Time elapsed from randomization to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.
measure: Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT)
timeFrame: Time elapsed from randomization to study treatment discontinuation or death. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.
measure: Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS.
timeFrame: Radiologic scans performed at baseline then every ~12 weeks for the first 72 weeks, then every ~24 weeks thereafter, assessed until disease progression. Assessed until 19 Sep 2016 DCO.
measure: To Determine the Exposure to Olaparib by Pharmacokinetic Analysis
timeFrame: Pharmacokinetics sampling to be performed in a subset of patients. Sampling times: Day 1 pre-dose & 1 hour; Day 15 pre-dose & 1 hour; Day 29 pre-dose. Assessed until 19 Sep 2016 DCO.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: Palo Alto Foundation Medical Group
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Orlando
country: United States
facility: Gynecologic Cancer Center
state: Florida
city: Evanston
country: United States
facility: North Shore University
state: Illinois
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Voorhees
country: United States
facility: MD Anderson at Cooper Cancer Center
state: New Jersey
city: Albany
country: United States
facility: Womens Cancer Care Associates
state: New York
city: Mineola
country: United States
facility: Winthrop Gynecologic Oncology Associates
state: New York
city: Hilliard
country: United States
facility: OSU JamesCare at Mill Run
state: Ohio
city: Nashville
country: United States
facility: Henry Joyce Cancer Clinic
state: Tennessee
city: Milwaukee
country: United States
facility: Aurora St Lukes Medical Center
state: Wisconsin
city: Heidelberg
country: Australia
facility: Mercy Hospital for Women
city: Parkville
country: Australia
facility: The Royal Womens Hospital
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: Gent
country: Belgium
facility: U.Z. Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Barretos
country: Brazil
facility: Centro Diagnóstico Barretos
city: Fortaleza
country: Brazil
facility: Centro Regional Integrado de Oncologia
city: Goiânia
country: Brazil
facility: Hospital Araujo Jorge
city: Ijuí
country: Brazil
facility: Hospital de Caridade de Ijuí
city: Itajai
country: Brazil
facility: Centro de Novos Tratamentos Itajai
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alagre
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base São José do Rio Preto
city: São Paulo
country: Brazil
facility: Centro de Referencia da Saude da Mulher
city: São Paulo
country: Brazil
facility: Instituto do Câncer de São Paulo
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Norte-Dame
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Site Fleurimont
state: Quebec
city: Quebec
country: Canada
facility: Hotel-Dieu de Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: The Tumor Hospital affiliated to China Medical Science Insti
city: Changchun
country: China
facility: 1st Hospital of Jilin university
city: Changchun
country: China
facility: Jilin Provincial Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital Affiliated to Sichuan University
city: Chongqing
country: China
facility: ChongQing Cancer Hospital
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Women's Hospital, Zhejaing University School of Medicine
city: Harbin
country: China
facility: The Tumour Hospital of Harbin Medical University
city: Huangzhou
country: China
facility: Zhejiang Cancer Hospital, Huangzhou
city: Ji Nan
country: China
facility: JINAN, Qi Lu Hosp. of SD Univ.
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Shanghai Cancer Hospital of Fudan University
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Xian
country: China
facility: First affiliated hospital college of XianJiaotong University
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen Cedex
country: France
facility: CAC François Baclesse
city: Lyon Cedex 08
country: France
facility: 69LYON, C Bérard, Onco
city: Nantes,
country: France
facility: Centre Catherine de Sienne
city: Paris Cedex 5
country: France
facility: Institut Curie Paris Et Saint Cloud
city: Paris
country: France
facility: 75PARIS, H Tenon, Onco
city: Paris
country: France
facility: Hopital Européen Georges Pompidou
city: Pierre Benite Cedex
country: France
facility: 69PIERREBE, CH Lyon Sud,
city: Saint Cloud
country: France
facility: 92STCLOUD, C Huguenin, Onco
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Helios-Kliniken Berlin - Buch
city: Erlangen
country: Germany
facility: Friedrich-Alexander-Universität Erlangen-Nürnberg
city: Essen
country: Germany
facility: Klinikum Essen-Mitte,Evang. Huyssens-Stiftung/Knapps gGmbH
city: Frankfurt
country: Germany
facility: Johann-Wolfgang Goethe-Universität
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität
city: Ravensburg
country: Germany
facility: Onkologie Ravensburg
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar Saba
country: Israel
facility: Sapir Medical Centre
city: Ramat Gan
country: Israel
facility: Tel Hashomer
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: Azienda Ospedaliera Policlinico Di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto Irccs
city: Roma
country: Italy
facility: Istituto Regina Elena-Polo Oncologico Ifo
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
city: Akashi-shi
country: Japan
facility: Hyogo Cancer Center
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Niigata-shi
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Grzepnica
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna
city: Olsztyn
country: Poland
facility: SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii
city: Olsztyn
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Olsztynie
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im Marii Sklodowskiej-Curie
city: Warszawa
country: Poland
facility: Szpital Specjalistyczny im. Swietej Rodziny SPZOZ
city: Moscow
country: Russian Federation
facility: Chemotherapy Department, Russian Cancer Research Centre
city: Saint Petersburg
country: Russian Federation
facility: St.Petersburg City Oncology Dispensary, Dept. Gynecology
city: St.Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
city: Barcelona
country: Spain
facility: Barcelona,H.Clinic i Provincial,Oncología
city: Barcelona
country: Spain
facility: Barcelona,H.de la Sta.Creu i S.Pau,Oncología
city: Córdoba
country: Spain
facility: Córdoba,H.Reina Sofía,Oncología
city: Gerona
country: Spain
facility: Gerona,H.Josep Trueta,Oncología
city: Madrid
country: Spain
facility: Madrid, H.C.S.Carlos,Oncología
city: Madrid
country: Spain
facility: Madrid,H.12 de Octubre,Oncología
city: Pamplona
country: Spain
facility: Hospital Provincial de Navarra
city: Valencia
country: Spain
facility: Valencia, IVO, Oncología
city: Valencia
country: Spain
facility: Valencia,H.C.U.Valencia,Oncología
city: Birmingham
country: United Kingdom
facility: City Hospital Birmingham Cancer Trials Team
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Coventry
country: United Kingdom
facility: Arden Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Research UK Centre
city: London
country: United Kingdom
facility: Cancer Research UK and UCL Cancer Trials Centre
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital and Institute of Cancer Research
Study officials:
affiliation: Universite de Paris Descartes, France
name: Professor E Pujade-Lauraine, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frenel JS, Kim JW, Aryal N, Asher R, Berton D, Vidal L, Pautier P, Ledermann JA, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Colombo N, Park-Simon TW, Tamura K, Sonke GS, Freimund AE, Lee CK, Pujade-Lauraine E. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial. Ann Oncol. 2022 Oct;33(10):1021-1028. doi: 10.1016/j.annonc.2022.06.011. Epub 2022 Jun 27.
citation: Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
citation: Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. doi: 10.1016/S1470-2045(21)00073-5. Epub 2021 Mar 18.
citation: Tjokrowidjaja A, Lee CK, Friedlander M, Gebski V, Gladieff L, Ledermann J, Penson R, Oza A, Korach J, Huzarski T, Manso L, Pisano C, Asher R, Lord SJ, Kim SI, Lee JY, Colombo N, Park-Simon TW, Fujiwara K, Sonke G, Vergote I, Kim JW, Pujade-Lauraine E. Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy. Eur J Cancer. 2020 Nov;139:59-67. doi: 10.1016/j.ejca.2020.08.021. Epub 2020 Sep 23.
citation: Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, Wenzel LB, Eek D, Rodrigues M, Clamp A, Penson RT, Provencher D, Korach J, Huzarski T, Vidal L, Salutari V, Scott C, Nicoletto MO, Tamura K, Espinoza D, Joly F, Pujade-Lauraine E. Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. Lancet Oncol. 2018 Aug;19(8):1126-1134. doi: 10.1016/S1470-2045(18)30343-7. Epub 2018 Jul 17.
citation: Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25.