Study 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.

Condition or Disease	Intervention/Treatment
Platinum Sensitive BRCA Mutated Relapsed Ovarian Cancer Following Complete or Partial Response to Platinum Based Chemotherapy	Drug: Olaparib 300mg tablets Drug: Placebo to match olaparib 300mg

Study Design

Study Type	Interventional
Actual Enrollment	327 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
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 Start Date	September 3, 2013
Actual Primary Completion Date	September 19, 2016
Anticipated Study Completion Date	December 31, 2024

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Olaparib 300mg tablets Taken orally twice daily	Drug: Olaparib 300mg tablets 300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.
Placebo tablets Taken orally twice daily	Drug: Placebo to match olaparib 300mg

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1) [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.]
   To determine the efficacy by progression free survival (PFS) (using investigator assessment according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)) of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Secondary Outcome Measures

1. Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival [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.]
   To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of overall survival (OS).
2. Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death [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.]
   To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy by assessment of time to earliest progression by RECIST or CA-125 or death.
3. Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression [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]
   To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization up to second progression
4. 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) [Questionnaires completed by patient at baseline, Day 29 and then every 12 weeks for 12 months. Assessed until 19 Sep 2016 DCO.]
   To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
5. Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST) [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.]
   To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to first subsequent therapy or death (TFST).
6. Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST) [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.]
   To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to second subsequent therapy or death (TSST).
7. Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT) [Time elapsed from randomization to study treatment discontinuation or death. Assessed until 03 Feb 2020 DCO; up to a maximum of 75 months.]
   To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to study treatment discontinuation or death (TDT).
8. Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS. [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.]
   To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).
9. To Determine the Exposure to Olaparib by Pharmacokinetic Analysis [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.]
   To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy

Eligibility Criteria

Ages Eligible for Study	18 Years to 130 Years (Adult, Older Adult)
Sexes Eligible for Study	Female
Accepts Healthy Volunteers	No
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.

Contacts and Locations

Sponsors and Collaborators	AstraZeneca, European Network of Gynaecological Oncological Trial Groups (ENGOT), Myriad Genetic Laboratories, Inc., Merck Sharp & Dohme LLC
	European Network of Gynaecological Oncological Trial Groups (ENGOT), Myriad Genetic Laboratories, Inc., Merck Sharp & Dohme LLC
Locations	University of Alabama at Birmingham | Birmingham, Alabama, United States, Palo Alto Foundation Medical Group | San Francisco, California, United States, University of Colorado | Aurora, Colorado, United States, The Hospital of Central Connecticut | New Britain, Connecticut, United States, Gynecologic Cancer Center | Orlando, Florida, United States, North Shore University | Evanston, Illinois, United States, Greater Baltimore Medical Center | Baltimore, Maryland, United States, Johns Hopkins | Baltimore, Maryland, United States, Dana Farber Cancer Institute | Boston, Massachusetts, United States, Massachusetts General Hospital | Boston, Massachusetts, United States, MD Anderson at Cooper Cancer Center | Voorhees, New Jersey, United States, Womens Cancer Care Associates | Albany, New York, United States, Winthrop Gynecologic Oncology Associates | Mineola, New York, United States, OSU JamesCare at Mill Run | Hilliard, Ohio, United States, Henry Joyce Cancer Clinic | Nashville, Tennessee, United States, Aurora St Lukes Medical Center | Milwaukee, Wisconsin, United States, Mercy Hospital for Women | Heidelberg, Australia, The Royal Womens Hospital | Parkville, Australia, Prince of Wales Hospital | Randwick, Australia, U.Z. Gent | Gent, Belgium, UZ Leuven Gasthuisberg | Leuven, Belgium, Centro Diagnóstico Barretos | Barretos, Brazil, Centro Regional Integrado de Oncologia | Fortaleza, Brazil, Hospital Araujo Jorge | Goiânia, Brazil, Hospital de Caridade de Ijuí | Ijuí, Brazil, Centro de Novos Tratamentos Itajai | Itajai, Brazil, Hospital de Clinicas de Porto Alegre | Porto Alegre, Brazil, Irmandade da Santa Casa de Misericordia de Porto Alagre | Porto Alegre, Brazil, Hospital de Base São José do Rio Preto | São José do Rio Preto, Brazil, Centro de Referencia da Saude da Mulher | São Paulo, Brazil, Instituto do Câncer de São Paulo | São Paulo, Brazil, Juravinski Cancer Centre | Hamilton, Ontario, Canada, London Health Sciences Centre | London, Ontario, Canada, Princess Margaret Cancer Centre | Toronto, Ontario, Canada, Sunnybrook Health Sciences Center | Toronto, Ontario, Canada, CHUM - Hopital Norte-Dame | Montreal, Quebec, Canada, CHUS Site Fleurimont | Sherbrooke, Quebec, Canada, Hotel-Dieu de Quebec | Quebec, Canada, Beijing Cancer Hospital | Beijing, China, The Tumor Hospital affiliated to China Medical Science Insti | Beijing, China, 1st Hospital of Jilin university | Changchun, China, Jilin Provincial Cancer Hospital | Changchun, China, Hunan Cancer Hospital | Changsha, China, West China Hospital Affiliated to Sichuan University | Chengdu, China, ChongQing Cancer Hospital | Chongqing, China, Research Site | Guangzhou, China, 510060 Women's Hospital, Zhejaing University School of Medicine | Hangzhou, China, The Tumour Hospital of Harbin Medical University | Harbin, China, Zhejiang Cancer Hospital, Huangzhou | Huangzhou, China, JINAN, Qi Lu Hosp. of SD Univ. | Ji Nan, China, Research Site | Shanghai, China, 200011 Shanghai Cancer Hospital of Fudan University | Shanghai, China, The First Affiliated Hospital of Soochow University | Suzhou, China, First affiliated hospital college of XianJiaotong University | Xian, China, Institut Bergonie | Bordeaux, France, CAC François Baclesse | Caen Cedex, France, 69LYON, C Bérard, Onco | Lyon Cedex 08, France, Centre Catherine de Sienne | Nantes,, France, Institut Curie Paris Et Saint Cloud | Paris Cedex 5, France, 75PARIS, H Tenon, Onco | Paris, France, Hopital Européen Georges Pompidou | Paris, France, 69PIERREBE, CH Lyon Sud, | Pierre Benite Cedex, France, 92STCLOUD, C Huguenin, Onco | Saint Cloud, France, Institut Claudius Regaud | Toulouse, France, Centre Alexis Vautrin | Vandoeuvre Les Nancy, France, Institut Gustave Roussy | Villejuif Cedex, France, Helios-Kliniken Berlin - Buch | Berlin, Germany, Friedrich-Alexander-Universität Erlangen-Nürnberg | Erlangen, Germany, Klinikum Essen-Mitte,Evang. Huyssens-Stiftung/Knapps gGmbH | Essen, Germany, Johann-Wolfgang Goethe-Universität | Frankfurt, Germany, Medizinische Hochschule Hannover | Hannover, Germany, Universitätsklinikum Schleswig-Holstein | Lübeck, Germany, Klinikum rechts der Isar der Technischen Universität | München, Germany, Onkologie Ravensburg | Ravensburg, Germany, Universitätsklinikum Rostock | Rostock, Germany, Rambam Health Care Campus | Haifa, Israel, Sapir Medical Centre | Kfar Saba, Israel, Tel Hashomer | Ramat Gan, Israel, Istituto Europeo di Oncologia | Milano, Italy, Azienda Ospedaliera Policlinico Di Modena | Modena, Italy, Istituto Nazionale Tumori Fondazione Pascale | Napoli, Italy, Istituto Oncologico Veneto Irccs | Padova, Italy, Istituto Regina Elena-Polo Oncologico Ifo | Roma, Italy, Policlinico Universitario A. Gemelli | Roma, Italy, Hyogo Cancer Center | Akashi-shi, Japan, National Cancer Center Hospital | Chuo-ku, Japan, National Hospital Organization Kyushu Cancer Center | Fukuoka, Japan, Saitama Medical University International Medical Center | Hidaka-shi, Japan, National Hospital Organization Shikoku Cancer Center | Matsuyama-shi, Japan, Niigata University Medical and Dental Hospital | Niigata-shi, Japan, Kindai University Hospital | Osakasayama-shi, Japan, Hokkaido University Hospital | Sapporo-shi, Japan, Shizuoka Cancer Center | Sunto-gun, Japan, Asan Medical Center | Seoul, Korea, Republic of, Gangnam Severance Hospital | Seoul, Korea, Republic of, Samsung Medical Center | Seoul, Korea, Republic of, Seoul National University Hospital | Seoul, Korea, Republic of, Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital | Amsterdam, Netherlands, Maastricht Universitair Medisch Centrum | Maastricht, Netherlands, Universitair Medisch Centrum St. Radboud | Nijmegen, Netherlands, Erasmus Medisch Centrum | Rotterdam, Netherlands, Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna | Grzepnica, Poland, SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii | Olsztyn, Poland, Wojewódzki Szpital Specjalistyczny w Olsztynie | Olsztyn, Poland, Centrum Onkologii Instytut im Marii Sklodowskiej-Curie | Warszawa, Poland, Szpital Specjalistyczny im. Swietej Rodziny SPZOZ | Warszawa, Poland, Chemotherapy Department, Russian Cancer Research Centre | Moscow, Russian Federation, St.Petersburg City Oncology Dispensary, Dept. Gynecology | Saint Petersburg, Russian Federation, Leningrad Regional Oncology Dispensary | St.Petersburg, Russian Federation, Barcelona,H.Clinic i Provincial,Oncología | Barcelona, Spain, Barcelona,H.de la Sta.Creu i S.Pau,Oncología | Barcelona, Spain, Córdoba,H.Reina Sofía,Oncología | Córdoba, Spain, Gerona,H.Josep Trueta,Oncología | Gerona, Spain, Madrid, H.C.S.Carlos,Oncología | Madrid, Spain, Madrid,H.12 de Octubre,Oncología | Madrid, Spain, Hospital Provincial de Navarra | Pamplona, Spain, Valencia, IVO, Oncología | Valencia, Spain, Valencia,H.C.U.Valencia,Oncología | Valencia, Spain, City Hospital Birmingham Cancer Trials Team | Birmingham, United Kingdom, Addenbrooke's Hospital | Cambridge, United Kingdom, Arden Cancer Centre | Coventry, United Kingdom, Edinburgh Cancer Research UK Centre | Edinburgh, United Kingdom, Cancer Research UK and UCL Cancer Trials Centre | London, United Kingdom, Royal Marsden Hospital | London, United Kingdom, The Christie NHS Foundation Trust | Manchester, United Kingdom, Royal Marsden Hospital and Institute of Cancer Research | Sutton, United Kingdom,
Investigators	Principal Investigator: Professor E Pujade-Lauraine, MD, PhD, Universite de Paris Descartes, France

More Information

Additional Information

• Redacted CSR synopsis

Publications

• 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.

• 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.

• 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. Erratum In: Lancet Oncol. 2024 Jul;25(7):e284. doi: 10.1016/S1470-2045(24)00317-6.

• 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.

• 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.

• 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. Erratum In: Lancet Oncol. 2017 Sep;18(9):e510. doi: 10.1016/S1470-2045(17)30639-3.

Additional Relevant MeSH Terms

• Ovarian Neoplasms
• Carcinoma, Ovarian Epithelial
• Hypersensitivity
• Endocrine Gland Neoplasms
• Neoplasms by Site
• Neoplasms
• 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
• Carcinoma
• Neoplasms, Glandular and Epithelial
• Neoplasms by Histologic Type
• Immune System Diseases