AzTrials
AzTrials

Borderline Ovarian Serous TumorPhase 2/3NCT02101788

Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

A Phase 2/3 study testing Letrozole, Paclitaxel and Pegylated Liposomal Doxorubicin Hydrochloride in people with Borderline Ovarian Serous Tumor and Micropapillary Serous Carcinoma, run by National Cancer Institute (NCI) at 501 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This phase II/III trial studies how well trametinib works and compares it to standard treatment with either letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan in treating patients with low-grade ovarian cancer or peritoneal cavity cancer that has come back (recurrent), become worse… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Letrozole, Paclitaxel and Pegylated Liposomal Doxorubicin Hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
260 participants
Where
501 sitesin 2 countries
Study dates
11 Apr 2014to 27 Oct 2025
Phase
Phase 2/3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients age greater than 18 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

501 sites in 2 countries.

313 sites in 2 countries

United States300 sites

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Southwest Gynecologic Oncology Associates Inc

    Albuquerque, New Mexico, 87106

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • New Mexico Cancer Research Alliance

    Albuquerque, New Mexico, 87131

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Cancer Care Center at Island Hospital

    Anacortes, Washington, 98221

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Virginia Mason Bainbridge Island Medical Center

    Bainbridge Island, Washington, 98110

  • Saint Alphonsus Cancer Care Center-Baker City

    Baker City, Oregon, 97814

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Flaget Memorial Hospital

    Bardstown, Kentucky, 40004

  • Woman's Hospital

    Baton Rouge, Louisiana, 70817

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • UHHS-Chagrin Highlands Medical Center

    Beachwood, Ohio, 44122

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Swedish Cancer Institute-Eastside Oncology Hematology

    Bellevue, Washington, 98005

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Saint Luke's University Hospital-Bethlehem Campus

    Bethlehem, Pennsylvania, 18015

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Boulder Community Foothills Hospital

    Boulder, Colorado, 80303

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Highline Medical Center-Main Campus

    Burien, Washington, 98166

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Oncology Specialists of Charlotte

    Charlotte, North Carolina, 28207

  • Southern Oncology Specialists-Charlotte

    Charlotte, North Carolina, 28262

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Cheyenne Regional Medical Center-West

    Cheyenne, Wyoming, 82001

  • Northwestern University

    Chicago, Illinois, 60611

  • Swedish Covenant Hospital

    Chicago, Illinois, 60625

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Sampson Radiation Oncology

    Clinton, North Carolina, 28328

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Community Cancer Institute

    Clovis, California, 93611

  • University Oncology Associates

    Clovis, California, 93611

  • Big Horn Basin Cancer Center

    Cody, Wyoming, 82414

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • John B Amos Cancer Center

    Columbus, Georgia, 31904

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Columbus NCI Community Oncology Research Program

    Columbus, Ohio, 43215

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • MD Anderson in The Woodlands

    Conroe, Texas, 77384

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Michiana Hematology Oncology PC-Crown Point

    Crown Point, Indiana, 46307

  • Northside Hospital-Forsyth

    Cumming, Georgia, 30041

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Sutter Davis Hospital

    Davis, California, 95616

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Delaware Radiation Oncology

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • National Jewish Health-Main Campus

    Denver, Colorado, 80206

  • The Women's Imaging Center

    Denver, Colorado, 80209

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Rose

    Denver, Colorado, 80220

  • Rose Medical Center

    Denver, Colorado, 80220

  • Western States Cancer Research NCORP

    Denver, Colorado, 80222

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Henry Ford River District Hospital

    East China, Michigan, 48054

  • Easton Hospital

    Easton, Pennsylvania, 18042

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Elkhart Clinic

    Elkhart, Indiana, 46514-2098

  • Michiana Hematology Oncology PC-Elkhart

    Elkhart, Indiana, 46514

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Saint Francis Hospital

    Evanston, Illinois, 60202

  • Deaconess Clinic Downtown

    Evansville, Indiana, 47713

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Virginia Mason Federal Way Medical Center

    Federal Way, Washington, 98002

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Palo Alto Medical Foundation-Fremont

    Fremont, California, 94538

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • Northeast Georgia Medical Center-Gainesville

    Gainesville, Georgia, 30501

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Tacoma/Valley Radiation Oncology Centers-Gig Harbor

    Gig Harbor, Washington, 98332

  • MultiCare Gig Harbor Medical Park

    Gig Harbor, Washington, 98335

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Mountain Blue Cancer Care Center

    Golden, Colorado, 80401

  • National Jewish Health-Western Hematology Oncology

    Golden, Colorado, 80401

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • Wayne Radiation Oncology

    Goldsboro, North Carolina, 27534

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Banner North Colorado Medical Center

    Greeley, Colorado, 80631

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Rocky Mountain Cancer Centers-Greenwood Village

    Greenwood Village, Colorado, 80111

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Henry Ford Saint John Hospital - Academic

    Grosse Pointe Woods, Michigan, 48236

  • Henry Ford Saint John Hospital - Breast

    Grosse Pointe Woods, Michigan, 48236

  • Henry Ford Saint John Hospital - Van Elslander

    Grosse Pointe Woods, Michigan, 48236

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • Sudarshan K Sharma MD Limited-Gynecologic Oncology

    Hinsdale, Illinois, 60521

  • Pulmonary Medicine Center of Chattanooga-Hixson

    Hixson, Tennessee, 37343

  • CHI Saint Vincent Cancer Center Hot Springs

    Hot Springs, Arkansas, 71913

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Hermann Texas Medical Center

    Houston, Texas, 77030

  • MD Anderson West Houston

    Houston, Texas, 77079

  • Novant Health Cancer Institute - Huntersville

    Huntersville, North Carolina, 28078

  • Southern Oncology Specialists-Huntersville

    Huntersville, North Carolina, 28078

  • Tennessee Valley Gynecologic Oncology

    Huntsville, Alabama, 35805

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana, 46260

  • Swedish Cancer Institute-Issaquah

    Issaquah, Washington, 98029

  • Allegiance Health

    Jackson, Michigan, 49201

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Onslow Memorial Hospital

    Jacksonville, North Carolina, 28546

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

  • Mercyhealth Hospital and Cancer Center - Janesville

    Janesville, Wisconsin, 53548

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo

    Kalamazoo, Michigan, 49048

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • Fred and Pamela Buffett Cancer Center - Kearney

    Kearney, Nebraska, 68845

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Kadlec Clinic Hematology and Oncology

    Kennewick, Washington, 99336

  • Northwest Cancer Clinic

    Kennewick, Washington, 99336

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Armstrong Center for Medicine and Health

    Kittanning, Pennsylvania, 16201

  • Community Howard Regional Health

    Kokomo, Indiana, 46904

  • IU Health La Porte Hospital

    La Porte, Indiana, 46350

  • Providence Regional Cancer System-Lacey

    Lacey, Washington, 98503

  • Rocky Mountain Cancer Centers-Lakewood

    Lakewood, Colorado, 80228

  • Saint Anthony Hospital

    Lakewood, Colorado, 80228

  • Saint Clare Hospital

    Lakewood, Washington, 98499

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Lancaster Radiation Oncology

    Lancaster, Ohio, 43130

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Women's Cancer Center of Nevada

    Las Vegas, Nevada, 89106

  • MD Anderson League City

    League City, Texas, 77573

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Geisinger Medical Oncology-Lewisburg

    Lewisburg, Pennsylvania, 17837

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • Saint Joseph Radiation Oncology Resource Center

    Lexington, Kentucky, 40504

  • Saint Joseph Hospital East

    Lexington, Kentucky, 40509

  • Saint Elizabeth Regional Medical Center

    Lincoln, Nebraska, 68510

  • Rocky Mountain Cancer Centers-Littleton

    Littleton, Colorado, 80120

  • AdventHealth Littleton

    Littleton, Colorado, 80122

  • Hope Cancer Clinic

    Livonia, Michigan, 48154

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Logan Regional Hospital

    Logan, Utah, 84321

  • Saint Joseph London

    London, Kentucky, 40741

  • Rocky Mountain Cancer Centers-Sky Ridge

    Lone Tree, Colorado, 80124

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Longmont United Hospital

    Longmont, Colorado, 80501

  • Rocky Mountain Cancer Centers-Longmont

    Longmont, Colorado, 80501

  • PeaceHealth Saint John Medical Center

    Longview, Washington, 98632

  • Jewish Hospital

    Louisville, Kentucky, 40202

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • Saints Mary and Elizabeth Hospital

    Louisville, Kentucky, 40215

  • UofL Health Medical Center Northeast

    Louisville, Kentucky, 40245

  • Banner McKee Medical Center

    Loveland, Colorado, 80539

  • Virginia Mason Lynnwood Medical Center

    Lynnwood, Washington, 98036

  • Henry Ford Saint John Hospital - Macomb Medical

    Macomb, Michigan, 48044

  • Henry Ford Warren Hospital - Breast Macomb

    Macomb, Michigan, 48044

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Saint Mary's Oncology/Hematology Associates of Marlette

    Marlette, Michigan, 48453

  • Matthews Radiation Oncology Center

    Matthews, North Carolina, 28105

  • Novant Health Cancer Institute - Matthews

    Matthews, North Carolina, 28105

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • UH Seidman Cancer Center at Landerbrook Health Center

    Mayfield Heights, Ohio, 44124

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • Idaho Urologic Institute-Meridian

    Meridian, Idaho, 83642

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • Jackson Memorial Hospital-Holtz Children's Hospital

    Miami, Florida, 33136

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Franciscan Saint Anthony Health-Michigan City

    Michigan City, Indiana, 46360

  • Woodland Cancer Care Center

    Michigan City, Indiana, 46360

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • Memorial Regional Cancer Center Day Road

    Mishawaka, Indiana, 46545

Other trials in United States

United Kingdom13 sites

  • Belfast City Hospital

    Belfast, Northern Ireland, BT9 7AB

  • Bristol Royal Infirmary

    Bristol, England, BS2 8ED

  • Addenbrookes Hospital-Medical School

    Cambridge, England, CB2 0QQ

  • Western General Hospital

    Edinburgh, Scotland, EH4 2XU

  • Beatson Oncology Center

    Glasgow, Scotland, G12 0YN

  • Saint Bartholomew's Hospital

    London, England, EC1A 7BE

  • Hammersmith Hospital

    London, England, W12 0HS

  • University College London Hospital

    London, England, WC1E 6AG

  • The Royal Marsden NHS Foundation Trust-Chelsea

    London, SW3 6JJ

  • Christie Hospital

    Manchester, England, M20 4BX

  • Nottingham City Hospital

    Nottingham, NG5 1PB

  • Musgrove Park Hospital

    Somerset, England, TA1 5DA

  • Saint James's University Hospital

    West Yorkshire, England, LS9 7TF

Other trials in United Kingdom

About this study

Official title: A Randomized Phase II/III Study to Assess the Efficacy of Trametinib (GSK 1120212) in Patients With Recurrent or Progressive Low-Grade Serous Ovarian Cancer or Peritoneal Cancer

This phase II/III trial studies how well trametinib works and compares it to standard treatment with either letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan in treating patients with low-grade ovarian cancer or peritoneal cavity cancer that has come back (recurrent), become worse (progressive), or spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is more effective than standard therapy in treating patients with ovarian or peritoneal cavity cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To estimate the progression-free survival (PFS) hazard ratio of trametinib compared to that of "commercially available therapies" consisting of one of five commercially available agents in women with recurrent low-grade serous carcinoma of the ovary or peritoneum previously treated with platinum-based chemotherapy.

SECONDARY OBJECTIVES:

  1. To determine the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4 for each treatment arm.

II. To determine the quality of life, as assessed by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O).

IIa. To compare trametinib to the control arm with regard to patients' self-reported acute (up to post-cycle 6) quality of life as measured by the FACT-O-Trial Outcome Index (TOI).

IIb. To compare trametinib to the control arm with regard to patients' self-reported acute (up to post-cycle 6) neurotoxicity as measured by the FACT-Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX).

III. To estimate the objective response rate (RR) of patients in each treatment arm.

IV. To test whether high expression of pERK, as quantified by immunohistochemistry (IHC), is associated with better prognosis (RR or PFS) among patients receiving the randomized treatment.

  1. To test whether genetic changes associated with MAPK pathway activation (KRAS, NRAS, HRAS, BRAF, MEK, ERBB2 or NF1) are associated with improved prognosis (RR or PFS) among patients receiving the randomized treatment.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive clinician's choice of either letrozole orally (PO) once daily (QD) on days 1-28, tamoxifen citrate PO twice daily (BID) on days 1-28, paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride (PLD) 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.

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.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Being tested
Letrozole, Paclitaxel, Pegylated Liposomal Doxorubicin Hydrochloride, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Cystadenocarcinoma, Serous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LetrozoleDrug

    Also called CGS 20267, CGS-20267, CGS20267, Femara

    Given PO

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Pegylated Liposomal Doxorubicin HydrochlorideDrug

    Also called ATI-0918, Caelyx, Dox-SL, Doxil

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Tamoxifen CitrateDrug

    Also called Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen

    Given PO

  • TopotecanDrug

    Also called Hycamptamine, Topotecan Lactone

    Given IV

  • Trametinib Dimethyl SulfoxideDrug

    Also called Mekinist, Meqsel, Spexotras

    Given PO

Study groups in NCT02101788
Study groupRoleWhat they receive
Arm A (letrozole, tamoxifen, paclitaxel, PLD, topotecan)Active comparatorPatients 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.
Receives: Drug: Letrozole; Drug: Paclitaxel; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tamoxifen Citrate; Drug: Topotecan
Arm B (trametinib)ExperimentalPatients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Quality-of-Life Assessment; Drug: Trametinib Dimethyl Sulfoxide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan.Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the PFS endpoint definition.

    Measured: Time from study entry to time of progression or death, an average of 7 months for arm A and 13 months for arm B

Secondary outcomes (7)

  1. Incidence of Adverse Events (AEs)

    Number of treated patients with Adverse Events (grade 3 or higher) observed while receiving randomized therapy. Excludes AEs observed among control patients treated with trametinib after crossover.Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the AE endpoint definition.

    Measured: During treatment period and up to 100 days after stopping the study treatment

  2. Overall Survival

    Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last follow-up were censored on the date of last contact. Patients with disease progression on the Control arm were allowed to cross over to the trametinib arm. Per the protocol, the intent-to-treat OS analysis was not adjusted for crossover.

    Measured: Time from study entry to time of death or date of last contact, an average of 29 months for arm A and 37 months for arm B

  3. Objective Tumor Response Rate (Complete Response and Partial Response)

    The Response Rates were estimated as the binomial proportion of patients with Best Overall Response of Complete or Partial response according to RECIST 1.1 criteria.

    Measured: Time from study entry to time of progression or death, an average of 7 months for arm A and 13 months for arm B

  4. Patients Reported Acute Quality of Life

    Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for ovarian cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). . The FACT-O TOI score is calculated as the sum of the subscale scores if more than 80% of the FACT-O TOI items provide valid answers and all of the component subscales have valid scores. The FACT-O TOI score ranges 0-100 with a large score suggesting better QOL. Participants were analyzed based on their group of assignment. Patients on Arm A who progressed were permitted to receive Arm B treatment. Study time for Arm A patients who crossed over was not included in the quality of life endpoint definition

    Measured: 1. baseline (prior to cycle 1), 12 weeks (prior to cycle 4), 24 weeks (4 weeks post cycle 6), 36 weeks post cycle 1, 52 weeks post cycle 1.

  5. Patient Reported Acute Peripheral Neuropathy Symptoms

    Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggesting less peripheral neuropathy symptoms

    Measured: Up to 52 weeks

  6. Progression Free Survival

    Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last followup were censored on the date of last CT Scan. RECIST v1.1 defines progression as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    Measured: Time from study entry to time of progression or death, an average of 7 months for SOC and 13 months for the treatment (Trametinib) arm.

  7. pERK Expression

    Will be quantified using the H-score derived from the immunohistochemistry analysis of patient tumor tissue and is expected to present as a continuous measure. will consider the prognostic and predictive abilities of pERK relative to objective response rate (ORR) or PFS. Analysis of the dichotomous markers will be supported by Kaplan Meier plots, and forest plots of the odds-ratio and hazard ratio estimates. Duration of response will be depicted using swimmer plots, with median duration estimated using Kaplan Meier methods. The multivariable models will include covariate adjustment for geographic region, performance status and number of prior regimens, presented using effect coding. The adjusted hazard- and odds- ratio estimates from the multivariable models will be supported by nominal p-values and 2-sided, 95% confidence intervals. Confidence intervals will be interpreted as the plausible range of values for the true (unobserved) ratio that is supported by the data.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2014 (estimated)
  2. Study start11 Apr 2014
  3. Primary completion4 Apr 2019
  4. Study completion27 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
260 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02101788
Sponsor's protocol ID
NCI-2014-00629
Other IDs
NCI-2014-00629, GOG-0281, GOG-0281, P50CA083639, U10CA180868
Status last verified
Jul 2026
First submitted
28 Mar 2014
Last updated
4 Aug 2026
Data monitoring committee
No

Publications

  • Gershenson DM, Miller A, Brady WE, Paul J, Carty K, Rodgers W, Millan D, Coleman RL, Moore KN, Banerjee S, Connolly K, Secord AA, O'Malley DM, Dorigo O, Gaillard S, Gabra H, Slomovitz B, Hanjani P, Farley J, Churchman M, Ewing A, Hollis RL, Herrington CS, Huang HQ, Wenzel L, Gourley C. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022 Feb 5;399(10324):541-553. doi: 10.1016/S0140-6736(21)02175-9.

    PubMed 35123694

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