Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.

Advanced Ovarian Cancer Clinical Trial

— SOLO-1  

Official title:

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer Following First Line Platinum Based Chemotherapy.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01844986
• Other study ID #: D0818C00001
• Secondary ID: 2013-001551-13
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 26, 2013
• Est. completion date: August 29, 2028

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

Description:

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients with BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer following First Line Platinum Based Chemotherapy

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: August 29, 2028
• Est. primary completion date: May 17, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Female patients with newly diagnosed, histologically confirmed, high risk advanced (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer and / or fallopian - tube cancer who have completed first line platinum based chemotherapy (intravenous or intraperitoneal).

• Stage III patients must have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery.

• 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 completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation:

• Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study.

• Patients must be randomized within 8 weeks of their last dose of chemotherapy

Exclusion Criteria:

• BRCA1 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 with early stage disease (FIGO Stage I, IIA, IIB or IIC)

• Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment.

• Patients where more than one debulking surgery has been performed before randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and interval debulking surgery are eligible).

• Patients who have previously been diagnosed and treated for earlier stage ovarian, fallopian tube or primary peritoneal cancer.

• Patients who have previously received chemotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease).

• Patients with synchronous primary endometrial cancer unless both of the following criteria are met: 1) stage <2 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 3 endometrioid adenocarcinoma OR = 60 years old at the time of diagnosis of endometrial cancer with Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.

Related Conditions & MeSH terms

• Advanced Ovarian Cancer
• BRCA Mutation
• Carcinoma, Ovarian Epithelial
• Complete Response
• FIGO Stage III-IV
• First Line Platinum Chemotherapy
• Newly Diagnosed
• Ovarian Neoplasms
• Partial Response

Intervention

Drug:
• Olaparib 300mg tablets
Olaparib/placebo tablets p.o 300mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Locations

Country	Name	City	State
Australia	Mercy Hospital for Women	Heidelberg
Australia	The Royal Womens Hospital	Parkville
Australia	Prince of Wales Hospital	Randwick
Brazil	Centro Diagnóstico Barretos	Barretos
Brazil	Hospital Araujo Jorge	Goiânia
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
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	CHUM - Hopital Norte-Dame	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Hotel-Dieu de Quebec	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
China	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	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	Obstetris and Gynecology Hospital of Fudan University	Shanghai
China	Shanghai Cancer Hospital of Fudan University	Shanghai
China	The First Affiliated Hospital of Soochow Universit	Suzhou
China	First affiliated hospital college of XianJiaotong University	Xian
France	Institut Bergonie	Bordeaux
France	CAC François Baclesse	Caen Cedex
France	69LYON, C Bérard, Onco	Lyon Cedex 08
France	Centre Catherine de Sienne	Nantes,
France	75PARIS, H Tenon, Onco	Paris
France	Centre Alexis Vautrin	Vandoeuvre Les Nancy
France	Institut Gustave Roussy	Villejuif Cedex
Israel	Rambam Health Care Campus	Haifa
Israel	Sapir Medical Centre	Kfar Saba
Israel	Rabin MC	Petach Tikva
Israel	Chaim Sheba Medical Centre	Tel Hashomer
Israel	Tel-Aviv Sourkasy Medical Center	Tel-Aviv
Italy	Bari- Istituto Tumori Giovanni Paolo II	Bari
Italy	Azienda Ospedaliera "Cannizzaro"	Catania
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Per Cura Tumori - Milano	Milano
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
Japan	Hyogo CC	Akashi-shi
Japan	National Cancer Center Hosp	Chuo-ku
Japan	NHO Kyushu CC	Fukuoka
Japan	Saitama Med. Univ. Int. Med. C	Hidaka-shi
Japan	NHO Shikoku Cancer Center	Matsuyama-shi
Japan	Niigata Univ. Med. Dent.	Niigata-shi
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Shizuoka Cancer Center	Sunto-gun
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea Cancer Center Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht
Poland	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
Russian Federation	Udmurtia Republic Clinical Oncology Center	Izhevsk
Russian Federation	Chemotherapy Department, Russian Cancer Research Centre	Moscow
Russian Federation	State Institution of Heath Omsk Regional Oncology Dispensary	Omsk
Russian Federation	Cancer Research Institute	Saint Petersburg
Russian Federation	St.Petersburg City Oncology Dispensary, Dept. Gynecology	Saint Petersburg
Russian Federation	Leningrad Regional Oncology Dispensary	St.Petersburg
Russian Federation	Research Institute of Oncology RAMS	Tomsk
Spain	Barcelona,H.Vall d´Hebrón,Oncología	Barcelona
Spain	Córdoba,H.Reina Sofía,Oncología	Córdoba
Spain	H.Llobregat,ICO-Duran i Reynals,Oncología	Hospitalet deLlobregat(Barcelo
Spain	Madrid, MD Anderson, Oncología	Madrid
Spain	Madrid,H.U.La Paz,Oncología	Madrid
Spain	Valencia, IVO, Oncología	Valencia
Spain	Valencia,H.C.U.Valencia,Oncología	Valencia
United Kingdom	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	Royal Marsden Hospital and Institute of Cancer Research	Sutton
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Women's Cancer Care Associates	Albany	New York
United States	University of New Mexico	Albuquerque	New Mexico
United States	McFarland Clinic, P.C.	Ames	Iowa
United States	Providence Cancer Center	Anchorage	Alaska
United States	Hope Women's Cancer Centers	Asheville	North Carolina
United States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	MD Anderson at Cooper Cancer Center	Camden	New Jersey
United States	Aultman Hospital	Canton	Ohio
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Univ Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospital Case Medical Center	Cleveland	Ohio
United States	South Carolina Oncology Associates, PA	Columbia	South Carolina
United States	Research Site	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Minnesota Oncology Hematology, PA	Edina	Minnesota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Univ of Connecticut Health Center	Farmington	Connecticut
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Gynecologic Oncology of West MI, PLLC	Grand Rapids	Michigan
United States	Aurora Baycare Medical Center	Green Bay	Wisconsin
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Texas Health Science Center of Houston	Houston	Texas
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Indiana University	Indianapolis	Indiana
United States	St. Vincent Hospital & Health Care Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Kettering Medical Center	Kettering	Ohio
United States	Womens Cancer Center of Nevada	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Norton Cancer Institute Research	Louisville	Kentucky
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Froedtert Memorial Hospital	Milwaukee	Wisconsin
United States	Northern Indiana Cancer Research Consortium	Mishawaka	Indiana
United States	Smilow Cancer Hospital at Yale New Haven	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center - New York	New York	New York
United States	Perlmutter Cancer Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Kaiser Permanente	Oakland	California
United States	Peggy and Charles Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Missouri Valley Cancer Consortium CCOP	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Gynecologic Cancer Center	Orlando	Florida
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	The University of Pennsylvania	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital & Medical Center	Phoenix	Arizona
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Mayo Clinic - Rochester, MN	Rochester	Minnesota
United States	Kaiser Permanente	Roseville	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Nancy N. & J.C. Lewis Cancer and Research Pavillion	Savannah	Georgia
United States	Maine Medical Partners	Scarborough	Maine
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Clinic Women's Health	Sioux Falls	South Dakota
United States	Stanford Women's Cancer Center	Stanford	California
United States	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Babak Edraki	Walnut Creek	California

Sponsors (4)

Lead Sponsor	Collaborator
AstraZeneca	GOG Foundation, Merck Sharp & Dohme LLC, Myriad Genetic Laboratories, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  France,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	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 high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.	Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. DCO: 17 May 2018
Secondary	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival	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 overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029.	Assessed every 4 weeks until treatment discontinues (up to a max of 156 weeks), then as per protocol. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Secondary	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death	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 to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death	CA-125 performed at baseline + every 4 weeks. Radiologic scans performed at baseline + every 12 weeks up to 156 weeks, then every 24 weeks until objective radiological disease progression. DCO:17May2018
Secondary	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression	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 randomisation to second progression (PFS2)	Following first progression disease then assessed per local practice every 12 weeks until second progression.
Secondary	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)	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 high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.	Questionnaires will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported
Secondary	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST)	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 randomisation to first subsequent therapy or death (TFST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).	Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Secondary	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST)	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 randomisation to second subsequent therapy or death (TSST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).	Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Secondary	Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT)	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 randomisation to study treatment discontinuation or death (TDT). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).	Time elapsed from randomization to study treatment discontinuation or death. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Secondary	Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS	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 potential future BRCA mutation assays (gene sequencing and large rearrangement analysis)	Radiologic scans performed at baseline then every 12 weeks for the first 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months.

External Links

•   Redacted Clinical Study Protocol
•   Redacted Statistical Analysis Plan
•   Redacted Statistical Analysis Plan