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

Sponsors

Lead Sponsor: Pfizer

Source Pfizer
Brief 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.

Overall Status Active, not recruiting
Start Date June 28, 2013
Completion Date September 30, 2021
Primary Completion Date April 1, 2016
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Demonstrate superior efficacy of study drug vs. physician's choice of selected chemotherapies in terms of increased progression-free survival. 3 years
Secondary Outcome
Measure Time Frame
Obtain additional estimates of the efficacy of study drug vs. physician's choice of selected chemotherapies in terms of overall survival, objective response rate, duration of response and disease control rate. 6 years
Characterize the safety profile of the study drug vs. physician's choice of selected chemotherapies in terms of adverse events and clinical laboratory tests. 3 years
Assess the effect on global health status of study drug vs. physician's choice of selected chemotherapies in terms of quality-of-life questionnaires. 3 years
Characterize the plasma pharmacokinetics (PK) of study drug in terms of plasma concentration-time profiles and model-based PK parameters. 3 years
Enrollment 360
Condition
Intervention

Intervention Type: Drug

Intervention Name: MEK162, MEK inhibitor; oral

Description: multiple dose, single schedule

Arm Group Label: MEK162

Intervention Type: Drug

Intervention Name: Physician's choice chemotherapy

Description: 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)

Arm Group Label: Physician's choice chemotherapy

Eligibility

Criteria:

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.

Gender: Female

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Pfizer CT.gov Call Center Study Director Pfizer
Location
Facility:
| Phoenix, Arizona, United States
| Scottsdale, Arizona, United States
| Irvine, California, United States
| Los Angeles, California, United States
| Aurora, Colorado, United States
| New Haven, Connecticut, United States
| Orlando, Florida, United States
| Tampa, Florida, United States
| West Palm Beach, Florida, United States
Georgia Regents University | Augusta, Georgia, 30912, United States
| Chicago, Illinois, United States
| Indianapolis, Indiana, United States
| Iowa City, Iowa, United States
| Baltimore, Maryland, United States
| Boston, Massachusetts, United States
| Detroit, Michigan, United States
| Grand Rapids, Michigan, United States
| Saint Louis, Missouri, United States
| Billings, Montana, United States
| Albuquerque, New Mexico, United States
| Bronx, New York, United States
| New York, New York, United States
| Cincinnati, Ohio, United States
| Cleveland, Ohio, United States
| Columbus, Ohio, United States
| Oklahoma City, Oklahoma, United States
| Philadelphia, Pennsylvania, United States
| Pittsburgh, Pennsylvania, United States
| Dallas, Texas, United States
| Houston, Texas, United States
| Charlottesville, Virginia, United States
Royal Adelaide Hospital | Adelaide, Australia
Western Health | Footscray, Australia
Sir Charles Gairdner Hospital | Nedlands, Australia
Mater Adult Hospital | South Brisbane, Australia
Sydney Adventist Hospital | Sydney, Australia
Burnside War Memorial Hospital | Toorak Gardens, Australia
Westmead Hospital | Westmead, Australia
University Clinic Innsbruck | Innsbruck, Austria
AKH Vienna | Vienna, Austria
Cliniques Universitaires Saint-Luc | Bruxelles, Belgium
Antwerp University Hospital | Edegem, Belgium
University Hospital Gent | Gent, Belgium
University Hospital Leuven | Leuven, Belgium
Centre Hospitalier de l' Ardenne | Libramont, Belgium
CHC Saint-Joseph | Liege, Belgium
CHR Citadelle | Liege, Belgium
Clinique Ste-Elisabeth | Namur, Belgium
Sint-Augustinus | Wilrijk, Belgium
| Calgary, Alberta, Canada
| Vancouver, British Columbia, Canada
| Winnipeg, Manitoba, Canada
| Hamilton, Ontario, Canada
| Toronto, Ontario, Canada
| Montreal, Quebec, Canada
CHUS - Hopital Fleurimont | Sherbrooke, Quebec, Canada
Masaryk Mamorial Cancer Institute | Brno, Czechia
Teaching Hospital Hradec Kralove | Hradec Kralove, Czechia
University Hospital | Olomouc, Czechia
Fakulni Nemocnice Ostrava | Ostrava-Poruba, Czechia
General University Hospital | Prague, Czechia
Hospital Na Bulovce, Institute of Radiation Oncology | Prague, Czechia
University Hospital | Aalborg, Denmark
Rigshospitalet | Copenhagen, Denmark
Department of Oncology | Harlev, Denmark
Tampere University Hospital | Tampere, Finland
Institut de Cancerologie de I'ouest Paul Papin | Angers, France
CHU Jean Minjoz | Besancon, France
Centre Oscar Lambret | Lille, France
Centre Leon Berard | Lyon, France
Institut Paoli Calmettes | Marseille, France
ICM | Montpellier, France
Centre Catherine de Sienne | Nantes, France
Hopital Europeen Georges Pompidou, rue Leblanc | Paris, France
Hopital Tenon | Paris, France
Clinique Armoricaine de Radiologie | Saint-Brieuc, France
ICO Gauducheau | Saint-Herblain, France
Hopitaux Universitaires de Strasbourg | Strasbourg, France
Institut Gustave Roussy | Villejuif, France
University Medical Center Aachen | Aachen, Germany
Charite Campus Virchow Klinikum - Frauenklinik | Berlin, Germany
University of Bonn - Department of Obstetrics and Gynecology | Bonn, Germany
Universitatsklinikum Carl Gustav Carus | Dresden, Germany
Frauenklinik University Hospital Erlangen | Erlangen, Germany
Kliniken Essen-Mitte, Evang. Huyssens Stiftung | Essen, Germany
University Hospital | Essen, Germany
University Hospital of Frankfurt | Frankfurt, Germany
University Clinic | Freiburg, Germany
Universitatsmedizin Gottingen | Gottingen, Germany
Uni-Medizin Greifswald | Greifswald, Germany
Medizinische Hochschule Hannover | Hannover, Germany
NCT - Gynecological Oncology Section - University Hospital | Heidelberg, Germany
Jena University Hospital - Department of Gynecology and Obstetrics | Jena, Germany
Klinikum Kassel | Kassel, Germany
Studienzentrale Gynakologische Onkologie | Kiel, Germany
UniversitatsKlinikum Schleswlg-Holstein | Lubeck, Germany
University Hospital of Giessen and Marburg | Marburg, Germany
Technical University Munich | Munich, Germany
Universitats-Frauenklinik | Tubingen, Germany
University Hopsital of Ulm | Ulm, Germany
Hungarian Defense Forces Medical Centre | Budapest, Hungary
National Institute of Oncology | Budapest, Hungary
Semmelweis University | Budapest, Hungary
Aladar Petz County Teaching Hospital | Gyor, Hungary
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato | Miskolc, Hungary
Josa Andras Oktatokorhaz | Nyiregyhaza, Hungary
St James University Hospital | Dublin, Ireland
Centro Riferimento Oncologico | Aviano, Italy
Azienda Ospedaliero-Universitaria Policlinico Consorziale | Bari, Italy
University Hospital Consortorium Policlinico di Bari | Bari, Italy
AOU Bologna | Bologna, Italy
Divisione di Ostetricia e Ginecologia | Brescia, Italy
Azienda Ospedaliera Cannizzaro | Catania, Italy
Hospital of Faenza | Faenza, Italy
Unita Operativa di Oncologia | Faenza, Italy
Instituto Europeo Oncologico | Milano, Italy
National Cancer Institute Milan | Milan, Italy
Ospedale Niguarda Ca' Granda | Milan, Italy
A.O.U. Federico II | Naples, Italy
Istituto Nazionale Tumori di Napoli | Naples, Italy
Clinica Ostetrica e Ginecologica, Universita di Pisa | Pisa, Italy
Agostino Gemelli Teaching Hospital | Roma, Italy
Policlinico Umberto I, Sapienza | Roma, Italy
Centre Hospitalier Emile Mayrisch | Esch-sur-Alzette, Luxembourg
AMC | Amsterdam, Netherlands
University Medical Center | Groningen, Netherlands
Maastricht University Medical Center+ | Maastricht, Netherlands
Haukland University Hospital | Bergen, Norway
Norwegian Radium Hospital | Oslo, Norway
University Hospital of the 'K. Marcinkowski' Medical University | Poznan, Poland
SPSK 2, Pomeranian Medical University | Szczecin, Poland
Wojskowy Instytut Medyczny - Centralny Szpital Kliniczny MON | Warszawa, Poland
Hosptial Nuestra Senora de Sonsoles | Avila, Spain
Hospital Duran i Reynals. Insitut Catala Oncologia | Barcelona, Spain
Hospital Moises Broggi | Barcelona, Spain
Hosptial Clinic de Barcelona | Barcelona, Spain
Hosptial Universitario Reina Sofia | Cordoba, Spain
Hospital 12 de Octubre, Madrid | Madrid, Spain
Hospital Ramon y Cajal | Madrid, Spain
Carlos Haya Hospital | Malaga, Spain
Hospital Universitario Central de Asturias | Oviedo, Spain
Hospital Son Llatzer | Palma de Mallorca, Spain
Hosptial Universitario Donostia | San Sebastian, Spain
Complejo Hospitalario | Santiago de Compostela, Spain
Hospital Univeritario Virgen Macarena | Sevilla, Spain
Hospital Virgen de la Salud | Toledo, Spain
The Valencian Institute of Oncology | Valencia, Spain
Karolinska University Hospital | Stockholm, Sweden
Kliniska provningar | Uppsala, Sweden
City Hospital | Birmingham, United Kingdom
Royal Marsden NHS Foundation Trust | London, United Kingdom
Sarah Cannon Research UK | London, United Kingdom
The Christie NHS Foundation Trust | Manchester, United Kingdom
Nottingham University Hospitals NHS Trust | Nottingham, United Kingdom
Royal Marsden NHS Foundation Trust | Sutton, United Kingdom
Location Countries

Australia

Austria

Belgium

Canada

Czechia

Denmark

Finland

France

Germany

Hungary

Ireland

Italy

Luxembourg

Netherlands

Norway

Poland

Spain

Sweden

United Kingdom

United States

Verification Date

June 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: MEK162

Type: Experimental

Label: Physician's choice chemotherapy

Type: Active Comparator

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov