A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

Low-grade Serous Ovarian Cancer Clinical Trial

Official title:

The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer): A Multinational, Randomized, Open-label Phase 3 Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Recurrent or Persistent Low-grade Serous Carcinomas of the Ovary, Fallopian Tube or Primary Peritoneum

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01849874
• Other study ID #: ARRAY-162-311
• Secondary ID: C42110032013-000
• Status: Terminated
• Phase: Phase 3
• Start date: June 27, 2013
• Est. completion date: August 23, 2022

Study information

• Verified date: October 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer) is a Phase 3 study during which patients with recurrent or persistent low-grade serous (LGS) carcinomas of the ovary, fallopian tube or primary peritoneum will receive either investigational study drug MEK162 or a chemotherapy chosen by the physician (liposomal doxorubicin, paclitaxel or topotecan). Patients will be followed to compare the effectiveness of the study drug to that of the selected chemotherapies. Patients may be eligible to crossover from physician's choice chemotherapy to MEK162 if they meet certain inclusion criteria including centrally confirmed disease progression. Approximately 360 patients from North America, Europe and Australia will be enrolled in this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 341
• Est. completion date: August 23, 2022
• Est. primary completion date: January 20, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Diagnosis of LGS carcinoma of the ovary, fallopian tube or primary peritoneum (invasive micropapillary serous carcinoma or invasive grade 1 serous carcinoma), confirmed histologically and verified by central pathology review.

• Recurrent or persistent measurable disease that has progressed (defined as radiological and/or clinical progression; an increase in cancer antigen [CA]-125 alone is not sufficient) on or after last therapy (i.e., chemotherapy, hormonal therapy, surgery) and is not amenable to potentially curative intent surgery, as determined by the patient's treating physician.

• Must have received at least 1 prior platinum-based chemotherapy regimen but have received no more than 3 lines of prior chemotherapy regimens, with no limit to the number of lines of prior hormonal therapy. Front-line therapy may include neoadjuvant and adjuvant therapy and will be counted as 1 prior systemic regimen. Biological therapy (e.g. bevacizumab) administered as a single agent is considered a prior systemic regimen and not a prior chemotherapy regimen. Maintenance therapy is not considered its own regimen but should be included with the regimen that it follows.

• Available archival tumor sample (excisional or core biopsy) for confirmation of LGS carcinoma diagnosis. If adequate archival tumor sample is not available, willingness to consent to tissue biopsy.

• Suitable for treatment with at least one of the physician's choice chemotherapy options (liposomal doxorubicin, paclitaxel or topotecan) as determined by the Investigator.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

• Additional criteria exist.

Key Exclusion Criteria:

• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).

• Prior therapy with a MEK or BRAF inhibitor.

• History of Gilbert's syndrome.

• Impaired cardiovascular function or clinically significant cardiovascular diseases.

• Uncontrolled or symptomatic brain metastases that are not stable or require steroids, are potentially life-threatening or have required radiation within 28 days prior to first dose of study treatment.

• Concomitant malignancies or previous malignancies with less than a 5-year disease-free interval at the time of first dose of study treatment; patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or ductal carcinoma in situ may be enrolled irrespective of the time of diagnosis.

• Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or active hepatitis C.

• Prior randomization into this clinical study.

• Additional criteria exist.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• Low-grade Serous Fallopian Tube Cancer
• Low-grade Serous Ovarian Cancer
• Low-grade Serous Peritoneal Cancer
• Ovarian Neoplasms

Intervention

Drug:
• MEK162, MEK inhibitor; oral
multiple dose, single schedule
• Physician's choice chemotherapy
Patients will receive one of the following chemotherapies as determined by the physician: Liposomal doxorubicin, anthracycline antibiotic; intravenous (multiple dose, single schedule) Paclitaxel, mitotic inhibitor; intravenous (multiple dose, single schedule) Topotecan, topoisomerase 1 inhibitor; intravenous (multiple dose, single schedule)

Locations

Country	Name	City	State
Australia	Adelaide Cardiology	Adelaide	South Australia
Australia	Adelaide Eye and Retina Centre	Adelaide	South Australia
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Thomas and Delaney Optometrists	Norwood	South Australia
Australia	Mater Misericordiae Health Services Brisbane Limited	South Brisbane	Queensland
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Burnside War Memorial Hospital	Toorak Gardens	South Australia
Australia	Dr Anil Arora	Wahroonga	New South Wales
Australia	Sydney Adventist Hospital	Wahroonga	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Innsbruck Medical University	Innsbruck	Tirol
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Ghent University Hospital	Gent
Belgium	University Hospital Gent	Gent
Belgium	University Hospital Leuven	Leuven	Vlaams-brabant
Belgium	Centre Hospitalier de l'ardenne	Libramont	Luxembourg
Belgium	Private practice Ophthalmology	Libramont	Luxembourg
Belgium	CHR de la Citadelle	Liege
Belgium	Clinique et Maternite Sainte-Elisabeth Namur	Namur
Belgium	Sint-Augustinus	Wilrijk
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer Center, Department of Oncology	Hamilton	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (Chum) - Hopital Notre-Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Czechia	Teaching Hospital Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Fakultni Nemocnice Ostrava	Ostrava - Poruba
Czechia	Fakultni nemocnice Ostrava	Ostrava-Poruba
Czechia	General University Hospital in Prague	Prague
Czechia	General University Hospital in Prague	Prague 2
Denmark	Aalborg Sygehus Apotek	Aalborg	North Jutland
Denmark	Aalborg University Hospital	Aalborg	North Jutland
Denmark	Herlev Hospital Onkologisk AFD	Herlev
Denmark	Region Hovedstadens Apotek	Kobenhavn o
Denmark	Rigshospitalet	Kobenhavn o
Denmark	Ojenklinikken 2061	København Ø
Denmark	Radiologisk Afdeling 2023	København Ø
Finland	Tampere University Hospital	Tampere
France	CHU Jean Minjoz	Besancon
France	Centre Oscar Lambret	Lille
France	Hopital Prive La Louviere	Lille
France	Hopital Edouard Herriot	Lyon
France	Centre Leon Berard	LYON Cedex 08
France	Centre Paradis Monticelli	Marseille
France	Institut Paoli Calmettes - Departement d'Oncologie Medicale	Marseille Cedex 09
France	Centre d'Ophtalmologie du LEZ Centre Medical Les Roques	Montferrier S/lez
France	Institut Regional du Cancer Montpellier	Montpellier CEDEX 5
France	Cabinet Liberal du Dr Xavier Zanlonghi	Nantes
France	Clinique Sourdille	Nantes
France	L'Hopital Prive du Confluent SAS	NANTES Cedex 2
France	Centre d'Investigations Cliniques 1423	Paris
France	Hopital Europeen Georges Pompidou	Paris Cedex 15
France	Centre Investigateur CARIO - HPCA	Plerin
France	Institut de Cancerologie de I'Ouest - Rene Gauducheau	Saint-Herblain Cedex
France	Institut Gustave Roussy	Villejuif Cedex
Germany	Charité Universitaetsmedizin Berlin	Berlin
Germany	Universitätsklinikum Bonn	Bonn	North-rhine Westphalia
Germany	Uni Carl Gustav Carus	Dresden	Saxony
Germany	Kliniken Essen-Mitte	Essen	North Rhine-westphalia
Germany	Universitaetsklinik Freiburg	Freiburg
Germany	Frauenheilkunde und Geburtshilfe	Greifswald
Germany	NCT Nationales Centrum für Tumorerkrankungen Heidelberg	Heidelberg
Germany	Klinik fur Frauenheilkunde und Geburtshilfe	Kassel	Hessen
Germany	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-holstein
Germany	Klinikum rechts der Isar	Munich	Bavaria
Germany	Universitaets-Brustzentrum	Tuebingen	Baden-wuerttemberg
Germany	Universitätsfrauenklinik Ulm	Ulm	Baden-wurttemberg
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont, Onkologiai Osztaly	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet Kozponti Aneszteziologiai es Intenzivterapias Osztaly	Budapest
Hungary	Orszagos Onkologiai Intezet, Nogyogyaszati Osztaly	Budapest
Hungary	Semmelweis Egyetem AOK Szemeszeti Klinika	Budapest
Hungary	Euromedic Diagnostics Magyarorszag Kft.	Gyor	Gyor-moson-sopron
Hungary	Petz Aladar Korhaz Kardiologiai Osztaly	Gyor	Gyor-moson-sopron
Hungary	Petz Aladar Korhaz Szemeszeti Osztaly	Gyor	Gyor-moson-sopron
Ireland	St James's Hospital	Dublin	Dublin 8
Italy	Centro di Riferimento Oncologico - Struttura Operativa Complessa (SOC)- Oncologia Medica C	Aviano	Pordenone
Italy	SSD Oncologia Medica Addarii-Zamagni - Policlinico S. Orsola-Malpighi	Bologna
Italy	Struttura Complessa di Oftalmologia Policlinico S. Orsola-Malpighi	Bologna
Italy	Spedali Civili Di Brescia	Brescia
Italy	Spedali Civili di Brescia - Struttura Complessa Clinicizzata - U.O.di Oculistica	Brescia
Italy	Azienda Ospedaliera Cannizzaro	Catania
Italy	Ospedale Civile degli Infermi - Servizio di Oculistica	Faenza	Ravenna
Italy	Ospedale Civile degli Infermi - Unita Operativa di Oncologia Medica	Faenza	Ravenna
Italy	Ospedale Umberto I - Unita Operativa di Oncologia	Lugo	Ravenna
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori - SC Oncologia Ginecologica	Milano
Italy	Istituto Europeo Oncologico	Milano
Italy	Ospedale San Raffaele - Unita Operativa di Oculistica	Milano
Italy	Azienda Ospedaliera Vincenzo Monaldi di Napoli - U.O.C. di Oculistica	Napoli
Italy	Istituto Nazionale Tumori di Napoli, "G.Pascale" , Oncologia Medica, Dipartimento Uro-Ginecologico	Napoli
Italy	Universita degli Studi Federico II di Napoli Dipartimento di Neuroscienze Scienze	Napoli
Italy	Universita degli Studi Federico II di Napoli Oncologia Medica	Napoli
Italy	Azienda Opsedaliera S. Maria Degli Angeli Pordenone-Dipartimento di Chirurgia Specialistica -	Pordenone
Italy	Ospedale Santa Maria delle Croci - Oculistica	Ravenna
Italy	Ospedale Santa Maria delle Croci - Unita Operativa di Oncologia	Ravenna
Italy	Azienda Ospedaliera Sant' Andrea - Unita Operativa Semplice di Patologia Vitreo-Retinica	Roma	Rome
Italy	Dipartimento di Scienze Chirurgiche per le Patologie della Testa e del Collo - UOC di Oculistica	Roma
Italy	Dipartimento Organi di Senso	Roma
Italy	Istituto Nazionale Tumori Regina Elena - Oncologia Medica A	Roma	RM
Italy	Policlinico Agostino Gemelli	Roma
Italy	Policlinico Umberto I - Università Sapienza	Roma	Rome
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Netherlands	Academic Medical Center (AMC)	Amsterdam	Noord-holland
Netherlands	University Medical Center Groningen, Medical Oncology	Groningen
Netherlands	Maastricht University Medical Centre	Maastricht
Norway	Aleris	Oslo
Norway	Avd. for gynekologisk kreft, Radiumhospitalet	Oslo
Norway	Oslo Universitetssykehus HF	Oslo
Poland	Centralny Szpital Kliniczny MON	Warsaw
Spain	Centro de Salud Anoeta	Anoeta	Guipuzcoa
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital de Sant Joan Despi Moises Broggi	Barcelona
Spain	Ophthalmology at Instituto Oftalmologico Integral	Barcelona
Spain	Cardiology at Consulta de Cardiologia	Cordoba
Spain	Centro Medico Sanitas Ressalta	Cordoba
Spain	Instituto de Oftalmologia y Hospital La Arruzafa	Cordoba
Spain	Radiology at Centro Medico Sanitas Ressalta	Cordoba
Spain	Hospital Universitario Reina Sofía/ Provincial	Córdoba	Castilla LA Mancha
Spain	Hospital Duran i Reynals	L'Hospitalet de Llobregat	Barcelona
Spain	Radiology at Hospital Univeristari de Bellvitge	L'Hospitalet de Llobregat
Spain	Hospital Ramón Y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Hospital Universitario Donostia	San Sebastian	Guipuzcoa
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Virgen de la Salud	Toledo
Spain	Fundacion IVO-Instituto Valenciano de Oncologia	Valencia
Spain	Ophthalmology at Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Sweden	Karolinska Universitetssjukhuset	Stockholm
Sweden	Onkologkliniken Akademiska Sjukhuset	Uppsala
United Kingdom	Ashtead Hospital	Ashtead	Surrey
United Kingdom	City Hospital	Birmingham	WEST Midlands
United Kingdom	The Clock House Medical Practice	Epsom	Surrey
United Kingdom	London Eye Diagnostic Centre	London
United Kingdom	Royal Marsden NHS Foundation Trust	London
United Kingdom	Sarah Cannon Research Institute UK	London	England
United Kingdom	The Harley Street Clinic	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	St. Anthony's Hospital	North Cheam	Sutton
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	Nottinghamshire
United Kingdom	University of Nottingham	Nottingham	Nottinghamshire
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	Eye Associates of New Mexico	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Georgia Regents University Cancer Center	Augusta	Georgia
United States	Rocky Mountain Lions Eye Institute	Aurora	Colorado
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Colorado Denver, University of Colorado Cancer Center	Aurora	Colorado
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Billings Clinic	Billings	Montana
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston (OCB)	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore Medical Center - Centennial Women's Health	Bronx	New York
United States	Montefiore Medical Center - Einstein Center for Cancer Care	Bronx	New York
United States	Montefiore Medical Center, Green Medical Arts Pavilion	Bronx	New York
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic-Main Campus	Cleveland	Ohio
United States	Fairview Hospital Moll Pavilion Cancer Center	Cleveland	Ohio
United States	James Cancer Hospital & Solove Research Institute	Columbus	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Stefanie Spielman Comprehensive Breast Cancer	Columbus	Ohio
United States	Parkland Health and Hospital System	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center-Clements University Hospital	Dallas	Texas
United States	UT Southwestern Medical Center-Zale Lipshy University Hospital	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Kresge Eye Institute	Detroit	Michigan
United States	Karmanos Cancer Institute	Farmington Hills	Michigan
United States	OSU Gynecologic Oncology at Mill Run	Hilliard	Ohio
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Associated Vitreoretinal and Uveitis Consultants	Indianapolis	Indiana
United States	St. Vincent Cancer Care	Indianapolis	Indiana
United States	St. Vincent Gynecologic Oncology	Indianapolis	Indiana
United States	St. Vincent Gynecology Oncology	Indianapolis	Indiana
United States	St. Vincent Hospital and Health Care Center, Inc.	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Admin.Office/Study Supplies Mailing Address: UCLA Medicine Hematology-Oncology	Los Angeles	California
United States	Doris Stein Research Center Building	Los Angeles	California
United States	Keck Hospital of USC	Los Angeles	California
United States	LAC & USC Medical Center	Los Angeles	California
United States	University of California Los Angeles, Hematology-Oncology Clinic	Los Angeles	California
United States	USC Healthcare Consultation Center 1	Los Angeles	California
United States	USC Healthcare Consultation Center 2	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Eye Physicians of Central Florida	Maitland	Florida
United States	Hillcrest Hospital	Mayfield Heights	Ohio
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	Gynecologic Oncology Associates	Newport Beach	California
United States	Dean McGee Eye Institute	Oklahoma City	Oklahoma
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Stephenson Cancer Center(clinic location)	Oklahoma City	Oklahoma
United States	University of California, Irvine/UC Irvine Health	Orange	California
United States	Eye Physicians of Central	Orlando	Florida
United States	Florida Hospital	Orlando	Florida
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jeanes Hospital	Philadelphia	Pennsylvania
United States	Associated Retina Consultants, Ltd.	Phoenix	Arizona
United States	University of Arizona Cancer Center	Phoenix	Arizona
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Center for Advanced Medicine	Saint Louis	Missouri
United States	Center For Clinical Studies	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	UCLA Hematology/Oncology Clinic - Santa Monica	Santa Monica	California
United States	Oncology Research Associates, PLLC d/b/a Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	UCLA Hematology Oncology Clinic Santa Clarita	Valencia	California
United States	Florida Cancer Specialists	Wellington	Florida
United States	University of Cincinnati Physicians Company	West Chester	Ohio
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	UCLA Hematology - Oncology Clinic - Westlake Village	Westlake Village	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Italy,  Netherlands,  Norway,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)	PFS was defined as the time from randomization to the earliest documented disease progression date or death due to any cause whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including Baseline) and an absolute increase of greater than or equal to (>=) 5 millimeter (mm). Appearance of new lesions >=10 mm in diameter also constituted PD. If a participant did not have an event at the time of the analysis cutoff or at the start of any new therapy, PFS was censored at the date of last adequate tumor assessment.	From randomization until documented progressive disease (PD) or death, whichever occurred first, for censored participants at the date of last adequate tumor assessment (up to 24 months)
Secondary	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. Participants who were alive at the data cutoff date were censored for overall survival at their last contact date.	From randomization date to the date of death, for censored participants at their last contact date (up to 24 months)
Secondary	Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST V1.1)	ORR was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR) (responders). CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 mm, PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Non-target lesions must be non-progressive disease.	From randomization until disease progression or death (up to 24 months)
Secondary	Duration of Response (DOR)	DOR was defined as the time from first radiographic evidence of response to the earliest documented progression date or death due to any cause, and was calculated on responders only. Responders with no PD or death date or subsequent anticancer therapy by the data cutoff date, were censored for DOR at their last radiological assessment. Responders who received subsequent anticancer therapy prior to PD or death were censored at their last radiological assessment prior to initiation of subsequent anticancer therapy.	From the first radiographic evidence of response to the first documentation of PD or death, for censored participants at their last radiological assessment (up to 24 months)
Secondary	Disease Control Rate (DCR)	Disease control rate was defined as percentage of participants with disease control. Disease control was defined as a best response of CR or PR, or stable disease (SD) documented at Week 24 or later. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm, and PR is defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the Baseline sum of diameters. Non-target lesions must be non-progressive disease. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study.	Week 24
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	From the first dose of study intervention until 30 days after the last dose (up to 9 years)
Secondary	Number of Participants With Shift Greater Than or Equal to Grade 3 From Baseline in Laboratory Parameter Values Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03	Number of participants with shifts from normal Baseline values (Grade 0) to abnormal post-baseline values on-study (shift to greater than or equal to Grade 3) were reported as per NCI-CTCAE, v4.03 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Shifts in lab parameter from Grade 0 to 3, Grade 0 to 4 and Grade 0 to Low 3 and 4 and Grade 0 to High 3 and 4 (for parameters total hemoglobin, lymphocytes, white blood cells, calcium, magnesium, potassium, and sodium) were reported.	From the first dose of study intervention until 30 days after the last dose (up to 9 years)
Secondary	Quality of Life Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)	EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a global health status/quality of life (QOL) scale, and 6 single-item scales. The global health status/QOL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for global health status/QOL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. In this study, global health status/QOL scale score was identified as the primary patient-reported outcome variable of interest. Physical functioning, emotional functioning, and social functioning scale scores were considered as secondary. Higher scores indicate better quality of life.	Screening, every 8 weeks from randomization for the first 72 weeks (while on treatment), treatment discontinuation visit, 30-day safety follow-up visit
Secondary	Quality of Life Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28)	EORTC QLQ-OV28 contains 28 items which assess a comprehensive range of relevant issues: abdominal/gastrointestinal (GI) symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal/menopausal symptoms, body image, attitude to disease/treatment and sexual functioning. The score for each domain and component score were scaled from 0 (minimum) to 100 (maximum). Higher scores indicate lower quality of life except for sexual functioning where higher scores indicate better quality of life.	Screening, every 8 weeks from randomization for the first 72 weeks (while on treatment), treatment discontinuation visit, 30-day safety follow-up visit
Secondary	Quality of Life Per Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX)	FACT/GOG-NTX questionnaire consists of questions for dimensions related to physical, social, emotional, and functional well-being which contains 11 items, with responses scored on a Likert scale from 0 (not at all) to 4 (very much) designed to capture the symptoms of chemotherapy-induced peripheral neuropathy (CIPN). The summed scores of each item were reverted into standardized scores ranging from 0 to 44, with a higher score indicating a lower level of neurological toxicity and less effect on quality of life (ie, higher scores indicate better quality of life). The trial outcome index consists of two subscales from the FACT-G: Physical Well Being (7 items) and Functional Well Being (7 items), plus the Cervix Cancer-specific subscale (15 items). Each item in the trial outcome index scored using a 5-point scale (0=not at all to 4=very much). The summed scores of each item were reverted into standardized scores ranging from 0 to 116. Higher scores indicate better quality of life.	Screening, every 8 weeks from randomization for the first 72 weeks (while on treatment), treatment discontinuation visit, 30-day safety follow-up visit
Secondary	Predose Plasma Concentration (Ctrough) of MEK162	Ctrough of MEK162 is defined as the predose plasma concentration of MEK162. Ctrough of MEK162 was observed directly from data.	Predose on Study Days 1, 57, and 113.
Secondary	Maximum Observed Plasma Concentration (Cmax) of MEK162	Cmax is maximum observed plasma concentration. Cmax of MEK162 was observed directly from data.	2 hours ± 10 minutes postdose on Study Days 1, 57, and 113.