Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer
Borderline Ovarian Serous Tumor, Micropapillary Serous Carcinoma, Ovarian Serous Adenocarcinoma

About this trial
This is an interventional treatment trial for Borderline Ovarian Serous Tumor
Eligibility Criteria
Inclusion Criteria:
Patients with the following tumors are included in the study:
- Patients initially diagnosed with low-grade serous ovarian or peritoneal carcinoma that recur as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, Federation of Obstetricians and Gynecologists [FIGO], World Health Organization [WHO] or Silverberg)
- Patients initially diagnosed with serous borderline ovarian or peritoneal carcinoma that recur as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO WHO or Silverberg)
- At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g. MAJOR: laparotomy, laparoscopy, thoracotomy, VATS [video assisted thorascopic surgery]); there is no restriction on MINOR procedures: (e.g. central venous catheter placement, ureteral stent placement or exchange, tumor core or fine-needle aspirate [FNA] biopsy)
- Patients must have documented low-grade serous carcinoma; confirmation must occur by prospective pathology review prior to study entry; the prospective pathology review can be done on tissue from the recurrent carcinoma or from original diagnostic specimen
- All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one target lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI; all imaging studies must be performed within 28 days prior to registration
Prior therapy
- Patients must have recurred or progressed following at least one platinum-based chemotherapy regimen
- Patients may have received an unlimited number of prior therapy regimens
- Patients may not have received all of the five choices in the "standard therapy" arm
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
- Any other prior therapy directed at the malignant tumor, including chemotherapy and radiation therapy, must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 28 days prior to registration
Trametinib, can cause fetal harm when administered to a pregnant woman; women of child-bearing potential (i.e. patients whose reproductive organs remain in place and who have not passed menopause) and men must agree to use a highly effective method of contraception (e.g. hormonal, intrauterine device or; abstinence*) prior to study entry, during the study participation, and for six months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to randomization, cannot be breast-feeding, and must agree to use a highly effective form of contraception throughout the treatment period and for 6 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Abstinence is only acceptable when this is in line with the preferred and usual lifestyle of the patient
- Patients must have the ability to understand and sign an approved informed consent and authorization permitting release of personal health information
- Patients must have a GOG performance status of 0 or 1
- Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome, bowel obstruction, or major resection of the stomach or bowel
- All prior treatment-related toxicities must be CTCAE v4 grade =< 1 (except alopecia) at the time of randomization
- Patients must have a left ventricular ejection fraction >= lower limit of normal by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
- Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min (within 14 days prior to treatment)
- Bilirubin =< 1.5 times upper limit of normal (within 14 days prior to treatment)
- Alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (within 14 days prior to treatment)
- Aspartate aminotransferase (AST) =< 2.5 times upper limit of normal (within 14 days prior to treatment)
- Albumin >= 2.5 g/dL (within 14 days prior to treatment)
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) =< 1.5 times upper limit of normal (within 14 days prior to treatment)
- Neutrophil count >= 1.5 x 10^9/L (within 14 days prior to treatment)
- Platelet count >= 100 x 10^9/L (within 14 days prior to treatment)
- Hemoglobin >= 9.0 g/dL (within 14 days prior to treatment)
- If letrozole is selected as the control therapy, patients must be postmenopausal, either following bilateral oophorectomy or at least 5 years after spontaneous menopause; patients within 5 years of spontaneous menopause or who have had a hysterectomy without bilateral oophorectomy must have postmenopausal luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels; patients on hormone replacement therapy (HRT) must agree to withdrawal of hormone therapy before letrozole is started
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib or standard of care agent
- If patients have had a potential index lesion radiated, it must have progressed post radiation therapy to be used as a measurable eligibility lesion
- Patients may not have received prior MEK, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), or v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor therapy
Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
- Patients may not be receiving any other anti-cancer or investigational agents
- Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to St. John's wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
- Patients with known leptomeningeal or brain metastases or spinal cord compression should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with a bowel obstruction or any other gastrointestinal condition that might affect absorption of the oral drug should be excluded; this would include patients with inability to swallow and retain orally-administered medication, malabsorption syndrome, or those with a major resection of the stomach or bowels
- Patients with a history of interstitial lung disease or pneumonitis
Patients with a previous or current malignancy at other sites should be excluded, with the exception of:
- Curatively treated local tumors such as carcinoma-in-situ of the cervix, basal or squamous cell carcinoma of the skin
- Tumors for which no relapse has been observed within 5 years
- Known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible); patients with human immunodeficiency virus (HIV) are not eligible if on anti-retroviral medications
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients, or to dimethyl sulfoxide (DMSO), or to Cremophor EL (polyoxyethylated castor oil); please note, exclusion for Cremophor is unnecessary unless paclitaxel is the only agent available and the patient randomizes to the conventional therapy option
Patients with a history or evidence of cardiovascular risk, including any of the following:
- Left ventricular ejection fraction (LVEF) < lower limit of normal (LLN)
- Bazett's corrected QT (QTcB) >= 480 msec
- History or evidence of current clinically significant uncontrolled arrhythmias
- Exception: Subjects with controlled atrial fibrillation for > 30 days prior to randomization are eligible
- History of (within 6 months prior to randomization) acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting
- History or evidence of current >= class II congestive heart failure as defined by New York Heart Association (NYHA)
- Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
- Patients with intra-cardiac defibrillators or permanent pacemakers
- Known cardiac metastases
- Patients with a history or current evidence/risk of retinal vein occlusion (RVO)
- Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
- Patients who require use of a concomitant medication that can prolong the QT interval
- Animal reproductive studies have not been conducted with trametinib; therefore, the study drug must not be administered to pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable)
Sites / Locations
- Tennessee Valley Gynecologic Oncology
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Fairbanks Memorial Hospital
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- CHI Saint Vincent Cancer Center Hot Springs
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Eden Hospital Medical Center
- Community Cancer Institute
- University Oncology Associates
- Sutter Davis Hospital
- Palo Alto Medical Foundation-Fremont
- Memorial Medical Center
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Sutter Cancer Research Consortium
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Sutter Medical Center Sacramento
- California Pacific Medical Center-Pacific Campus
- UCSF Medical Center-Mission Bay
- Stanford Cancer Center South Bay
- Palo Alto Medical Foundation-Santa Cruz
- Sutter Pacific Medical Foundation
- Palo Alto Medical Foundation-Sunnyvale
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Sutter Solano Medical Center/Cancer Center
- Rocky Mountain Cancer Centers-Aurora
- The Medical Center of Aurora
- Boulder Community Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Denver Health Medical Center
- National Jewish Health-Main Campus
- The Women's Imaging Center
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-Midtown
- SCL Health Saint Joseph Hospital
- Rocky Mountain Cancer Centers-Rose
- Rose Medical Center
- Western States Cancer Research NCORP
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center - Swedish
- Swedish Medical Center
- Mountain Blue Cancer Care Center
- National Jewish Health-Western Hematology Oncology
- North Colorado Medical Center
- Rocky Mountain Cancer Centers-Greenwood Village
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Rocky Mountain Cancer Centers-Sky Ridge
- Sky Ridge Medical Center
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- National Jewish Health-Northern Hematology Oncology
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Hartford Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- The Hospital of Central Connecticut
- Sibley Memorial Hospital
- UM Sylvester Comprehensive Cancer Center at Coral Gables
- UM Sylvester Comprehensive Cancer Center at Deerfield Beach
- Jackson Memorial Hospital-Holtz Children's Hospital
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- UM Sylvester Comprehensive Cancer Center at Plantation
- Northside Hospital
- John B Amos Cancer Center
- Northside Hospital-Forsyth
- Northeast Georgia Medical Center-Gainesville
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - Boise
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Walter Knox Memorial Hospital
- Saint Luke's Cancer Institute - Fruitland
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Kootenai Cancer Clinic
- Saint Luke's Cancer Institute - Twin Falls
- Rush - Copley Medical Center
- Northwestern University
- Swedish Covenant Hospital
- Carle at The Riverfront
- Carle Physician Group-Effingham
- NorthShore University HealthSystem-Evanston Hospital
- Saint Francis Hospital
- Northwestern Medicine Cancer Center Delnor
- NorthShore University HealthSystem-Glenbrook Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Sudarshan K Sharma MD Limited-Gynecologic Oncology
- Carle Physician Group-Mattoon/Charleston
- Good Samaritan Regional Health Center
- North Shore Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Rush-Copley Healthcare Center
- Michiana Hematology Oncology PC-Crown Point
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Deaconess Clinic Downtown
- Indiana University/Melvin and Bren Simon Cancer Center
- Ascension Saint Vincent Indianapolis Hospital
- Community Howard Regional Health
- IU Health La Porte Hospital
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Memorial Regional Cancer Center Day Road
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Chancellor Center for Oncology
- Michiana Hematology Oncology PC-Plymouth
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des Moines
- Broadlawns Medical Center
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- Methodist West Hospital
- Mercy Medical Center-West Lakes
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Saint Joseph London
- Jewish Hospital
- The James Graham Brown Cancer Center at University of Louisville
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Woman's Hospital
- Maine Medical Center- Scarborough Campus
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Baystate Medical Center
- Saint Joseph Mercy Hospital
- Bronson Battle Creek
- Saint Joseph Mercy Brighton
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
- Saint Joseph Mercy Canton
- Trinity Health IHA Medical Group Hematology Oncology - Canton
- Caro Cancer Center
- Saint Joseph Mercy Chelsea
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
- Hematology Oncology Consultants-Clarkston
- Newland Medical Associates-Clarkston
- Beaumont Hospital - Dearborn
- Ascension Saint John Hospital
- Great Lakes Cancer Management Specialists-Doctors Park
- Genesee Cancer and Blood Disease Treatment Center
- Genesee Hematology Oncology PC
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Spectrum Health at Butterworth Campus
- Trinity Health Grand Rapids Hospital
- Academic Hematology Oncology Specialists
- Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
- Michigan Breast Specialists-Grosse Pointe Woods
- Allegiance Health
- West Michigan Cancer Center
- Borgess Medical Center
- Sparrow Hospital
- Hope Cancer Clinic
- Trinity Health Saint Mary Mercy Livonia Hospital
- Great Lakes Cancer Management Specialists-Macomb Medical Campus
- Michigan Breast Specialists-Macomb Township
- Saint Mary's Oncology/Hematology Associates of Marlette
- Monroe Cancer Center
- Trinity Health Muskegon Hospital
- Lakeland Hospital Niles
- 21st Century Oncology-Pontiac
- Hope Cancer Center
- Newland Medical Associates-Pontiac
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- Great Lakes Cancer Management Specialists-Rochester Hills
- Ascension Saint Mary's Hospital
- Oncology Hematology Associates of Saginaw Valley PC
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Bhadresh Nayak MD PC-Sterling Heights
- Ascension Saint Joseph Hospital
- Munson Medical Center
- Advanced Breast Care Center PLLC
- Great Lakes Cancer Management Specialists-Macomb Professional Building
- Macomb Hematology Oncology PC
- Michigan Breast Specialists-Warren
- Saint John Macomb-Oakland Hospital
- Saint Mary's Oncology/Hematology Associates of West Branch
- University of Michigan Health - West
- Huron Gastroenterology PC
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
- Sanford Joe Lueken Cancer Center
- University of Mississippi Medical Center
- Central Care Cancer Center - Bolivar
- Cox Cancer Center Branson
- Freeman Health System
- Mercy Hospital Joplin
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Saint Louis Cancer and Breast Institute-South City
- Barnes-Jewish Hospital
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Nebraska Methodist Hospital
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Women's Cancer Center of Nevada
- Center of Hope at Renown Medical Center
- Renown Regional Medical Center
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Cooper Hospital University Medical Center
- Hackensack University Medical Center
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Rutgers Cancer Institute of New Jersey
- University of New Mexico Cancer Center
- Southwest Gynecologic Oncology Associates Inc
- New Mexico Cancer Research Alliance
- Roswell Park Cancer Institute
- NYP/Weill Cornell Medical Center
- University of Rochester
- Dickstein Cancer Treatment Center
- UNC Lineberger Comprehensive Cancer Center
- Novant Health Presbyterian Medical Center
- Oncology Specialists of Charlotte
- Southern Oncology Specialists-Charlotte
- Sampson Radiation Oncology
- Southeastern Medical Oncology Center-Clinton
- Duke University Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Wayne Radiation Oncology
- Novant Health Cancer Institute - Huntersville
- Southern Oncology Specialists-Huntersville
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Matthews Radiation Oncology Center
- Novant Health Cancer Institute - Matthews
- Novant Health Cancer Institute - Mooresville
- Duke Women's Cancer Care Raleigh
- Duke Raleigh Hospital
- Sanford Bismarck Medical Center
- Sanford Broadway Medical Center
- Sanford Clinic North-Fargo
- Sanford Roger Maris Cancer Center
- UHHS-Chagrin Highlands Medical Center
- Strecker Cancer Center-Belpre
- Adena Regional Medical Center
- University of Cincinnati Cancer Center-UC Medical Center
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Grandview Hospital
- Delaware Health Center-Grady Cancer Center
- Delaware Radiation Oncology
- Grady Memorial Hospital
- Fairfield Medical Center
- Lancaster Radiation Oncology
- Marietta Memorial Hospital
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Landerbrook Health Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Southern Ohio Medical Center
- Springfield Regional Medical Center
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- University Hospitals Sharon Health Center
- Saint Ann's Hospital
- UHHS-Westlake Medical Center
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences Center
- Mercy Hospital Oklahoma City
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Alphonsus Medical Center-Baker City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Legacy Mount Hood Medical Center
- Providence Newberg Medical Center
- Saint Alphonsus Medical Center-Ontario
- Providence Willamette Falls Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Saint Luke's University Hospital-Bethlehem Campus
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical Center
- Easton Hospital
- Geisinger Medical Center-Cancer Center Hazleton
- Armstrong Center for Medicine and Health
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- University of Pennsylvania/Abramson Cancer Center
- West Penn Hospital
- Geisinger Cancer Services-Pottsville
- Geisinger Medical Group
- Chester County Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- Women and Infants Hospital
- Gibbs Cancer Center-Gaffney
- Saint Francis Hospital
- Saint Francis Cancer Center
- Gibbs Cancer Center-Pelham
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Memorial GYN Plus
- Saint Joseph Regional Cancer Center
- MD Anderson in The Woodlands
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Houston Methodist Hospital
- M D Anderson Cancer Center
- Memorial Hermann Texas Medical Center
- MD Anderson West Houston
- MD Anderson League City
- MD Anderson in Sugar Land
- Houston Methodist Sugar Land Hospital
- American Fork Hospital / Huntsman Intermountain Cancer Center
- Sandra L Maxwell Cancer Center
- Logan Regional Hospital
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Saint George Regional Medical Center
- Utah Cancer Specialists-Salt Lake City
- LDS Hospital
- Providence Regional Cancer System-Aberdeen
- Cancer Care Center at Island Hospital
- MultiCare Auburn Medical Center
- Virginia Mason Bainbridge Island Medical Center
- Overlake Medical Center
- Swedish Cancer Institute-Eastside Oncology Hematology
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Virginia Mason Federal Way Medical Center
- Saint Francis Hospital
- Tacoma/Valley Radiation Oncology Centers-Gig Harbor
- MultiCare Gig Harbor Medical Park
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and Oncology
- Northwest Cancer Clinic
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Virginia Mason Lynnwood Medical Center
- Jefferson Healthcare
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Peninsula Cancer Center
- MultiCare Good Samaritan Hospital
- Tacoma/Valley Radiation Oncology Centers-Puyallup
- Virginia Mason Medical Center
- Minor and James Medical PLLC
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- FHCC South Lake Union
- Fred Hutchinson Cancer Research Center
- Kaiser Permanente Washington
- Swedish Medical Center-Cherry Hill
- Swedish Medical Center-First Hill
- University of Washington Medical Center - Northwest
- Women's Cancer Center of Seattle
- University of Washington Medical Center - Montlake
- Providence Regional Cancer System-Shelton
- MultiCare Deaconess Cancer and Blood Specialty Center - Valley
- MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
- MultiCare Deaconess Cancer and Blood Specialty Center - North
- Tacoma/Valley Radiation Oncology Centers-Jackson Hall
- Franciscan Research Center-Northwest Medical Plaza
- MultiCare Tacoma General Hospital
- Northwest Medical Specialties PLLC
- Northwest NCI Community Oncology Research Program
- Tacoma/Valley Radiation Oncology Centers-Saint Joe's
- PeaceHealth Southwest Medical Center
- Legacy Salmon Creek Hospital
- Providence Saint Mary Regional Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Providence Regional Cancer System-Yelm
- Aurora Cancer Care-Southern Lakes VLCC
- Aurora Health Center-Fond du Lac
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Aurora BayCare Medical Center
- Mercyhealth Hospital and Cancer Center - Janesville
- Aurora Cancer Care-Kenosha South
- Aurora Bay Area Medical Group-Marinette
- Aurora Cancer Care-Milwaukee
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Vince Lombardi Cancer Clinic - Oshkosh
- Aurora Cancer Care-Racine
- Vince Lombardi Cancer Clinic-Sheboygan
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- Aurora Cancer Care-Waukesha
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
- Cheyenne Regional Medical Center-West
- Big Horn Basin Cancer Center
- Billings Clinic-Cody
- Welch Cancer Center
- Bristol Royal Infirmary
- Addenbrookes Hospital-Medical School
- Saint Bartholomew's Hospital
- Hammersmith Hospital
- University College London Hospital
- Christie Hospital
- Musgrove Park Hospital
- Saint James's University Hospital
- Belfast City Hospital
- Western General Hospital
- Beatson Oncology Center
- The Royal Marsden NHS Foundation Trust-Chelsea
- Nottingham City Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm A (letrozole, tamoxifen, paclitaxel, PLD, topotecan)
Arm B (trametinib)
Patients receive clinician's choice of either letrozole PO QD on days 1-28, tamoxifen citrate PO BID on days 1-28, paclitaxel IV over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or topotecan IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients developing progressive disease may cross over to Arm B.
Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.