Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery (S1310)
Adult Cholangiocarcinoma, Advanced Adult Hepatocellular Carcinoma, BCLC Stage C Adult Hepatocellular Carcinoma
About this trial
This is an interventional treatment trial for Adult Cholangiocarcinoma
Eligibility Criteria
Inclusion Criteria:
- DISEASE RELATED CRITERIA
- Patients must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease; patients with ampullary carcinoma are not eligible
- Patients must have measurable disease; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
- PRIOR/CONCURRENT THERAPY CRITERIA
Patients must have completed any prior chemotherapy at least 21 days prior to registration and have recovered from any of the effects AND
- Patients must have experienced progression to no more than 1 prior regimen of systemic chemotherapy for advanced biliary cancer OR
- Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible; if patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing one regimen of systemic chemotherapy used to treat the (unresectable or metastatic) disease recurrence
- Patients must not have been treated with prior MEK inhibitors; prior 5-FU or capecitabine treatment is allowed only if given as a radiosensitizer concurrently with radiation therapy at least 12 weeks prior to registration or if given as part of any adjuvant therapy regimen >= 12 months prior to study enrollment
- Patients must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy (including herbal or natural supplements) for treatment of cancer while on this treatment protocol
For patients who have received prior cryotherapy, radiation therapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:
- 28 days have elapsed since that therapy (lesions that have not been treated with local therapy must be present and measureable)
- CLINICAL/LABORATORY CRITERIA
- Patients must have a Zubrod performance status of 0-1
- Absolute neutrophil count (ANC) > 1000/mcL
- Platelets > 100000/mcL
- Total bilirubin =< 2.0 x the institutional upper limit of normal limits (IULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN; if liver metastases are present, AST and ALT must be =< 5 x IULN
- If the patient has had decompression of the biliary tree within the last 14 days, stability of the bilirubin level needs to be confirmed with two measurements that are within 5 to 7 days of each other; (the second measurement must be obtained within 7 days prior to registration;) both the first and second measurement must be =< 2.0 x IULN; stability is defined as the second measurement being no more than one point higher than the first
Patients must have adequate kidney function as evidenced by at least ONE of the following:
- Serum creatinine =< 1.5 x IULN within 28 days prior to registration
- Calculated creatinine clearance >= 50 ml/min for patients with creatinine level of 1.0-1.5 x IULN; the serum creatinine value used in the calculation must have been obtained within 28 days prior to registration
Patients with known history or current evidence of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) are not eligible:
- History of RVO or RPED, or predisposing factors to RVO or RPED (e.g. such as uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as:
- Evidence of new optic disc cupping
- Evidence of new visual field defects
- Intraocular pressure > 21 mmHg
- NOTE: ophthalmic exam is required for all patients; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration
- Patients must have echocardiogram and left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) within 28 days prior to registration; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration
- Patients must not have uncontrolled or clinically significant cardiovascular disease including: myocardial infarction within past 6 months; uncontrolled angina within past 6 months; class II-IV New York Heart Association (NYHA) congestive heart failure; grade 3 cardiac valve dysfunction; cardiac arrhythmia not controlled by medication; history of stroke or transient ischemic attack within 6 months; history of arterial thrombotic event (ATE) of any type in the past 6 months; treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled with anti-hypertensive therapy; known intra-cardiac defibrillators; known cardiac metastases
- Patients must have an electrocardiogram (ECG) within 28 days prior to registration; patients must have corrected QT interval (QTc) =< 500 msec; this exam should not be performed until or unless it is very clear the patient is otherwise eligible for registration
- Must be 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 or major resection of the stomach or bowels
- Must not have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO) or other agents used in study
- Must not have active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (patients with chronic or cleared HBV and HCV infection are eligible)
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method while on study and for 4 months after discontinuation of study drug; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
- SPECIMEN SUBMISSION CRITERIA
- Patients must submit paraffin-embedded tissue and blood for banking within 28 days after registration; paraffin-embedded tissue from prior surgical resection or from a diagnostic biopsy is acceptable
- REGULATORY CRITERIA
- Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Sites / Locations
- Alaska Breast Care and Surgery LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Kaiser Permanente-Anaheim
- Sutter Auburn Faith Hospital
- Kaiser Permanente-Baldwin Park
- Kaiser Permanente-Bellflower
- Alta Bates Summit Medical Center-Herrick Campus
- Mills - Peninsula Hospitals
- Sutter Davis Hospital
- City of Hope Comprehensive Cancer Center
- Kaiser Permanente Hospital
- Kaiser Permanente - Harbor City
- Kaiser Permanente-Irvine
- Kaiser Permanente Los Angeles Medical Center
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Kaiser Permanente-Cadillac
- Fremont - Rideout Cancer Center
- Memorial Medical Center
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Sutter Cancer Research Consortium
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Palo Alto Medical Foundation Health Care
- Kaiser Permanente - Panorama City
- Kaiser Permanente-Riverside
- Sutter Roseville Medical Center
- Sutter General Hospital
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente-San Diego Mission
- Kaiser Permanente-San Diego Zion
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Marcos
- Palo Alto Medical Foundation-Santa Cruz
- Sutter Pacific Medical Foundation
- Palo Alto Medical Foundation-Sunnyvale
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente
- University of Colorado Cancer Center - Anschutz Cancer Pavilion
- Memorial Hospital Colorado Springs
- Smilow Cancer Hospital-Derby Care Center
- Medical Oncology and Hematology Group PC-Guilford
- Smilow Cancer Hospital Care Center at Saint Francis
- Yale University
- Yale-New Haven Hospital North Haven Medical Center
- Smilow Cancer Hospital-Orange Care Center
- Charlotte Hungerford Hospital Center for Cancer Care
- Smilow Cancer Hospital-Waterbury Care Center
- University of Florida
- Moffitt Cancer Center
- Saint Alphonsus Cancer Care Center-Boise
- Kootenai Medical Center
- Kootenai Cancer Center
- Kootenai Cancer Clinic
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Cancer Care Center of Decatur
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Loyola University Medical Center
- Good Samaritan Regional Health Center
- Illinois CancerCare-Ottawa Clinic
- Radiation Oncology of Northern Illinois
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Reid Health
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Newman Regional Health
- Cancer Center of Kansas - Fort Scott
- Saint Catherine Hospital
- Saint Rose Ambulatory and Surgery Center
- Hays Medical Center
- Cancer Center of Kansas-Independence
- University of Kansas Cancer Center-West
- University of Kansas Cancer Center
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas-Manhattan
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Olathe Medical Center
- University of Kansas Cancer Center-Overland Park
- Cancer Center of Kansas - Parsons
- Via Christi Hospital-Pittsburg
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Salina Regional Health Center
- Saint Francis Hospital and Medical Center - Topeka
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Cancer Center of Kansas - Wichita
- Via Christi Regional Medical Center
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Oncology Hematology Care Inc-Crestview
- Boston Medical Center
- Lahey Hospital and Medical Center
- Saint Joseph Mercy Hospital
- Michigan Cancer Research Consortium NCORP
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Beaumont Hospital-Dearborn
- Wayne State University/Karmanos Cancer Institute
- Saint John Hospital and Medical Center
- Weisberg Cancer Treatment Center
- Hurley Medical Center
- Genesys Hurley Cancer Institute
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Allegiance Health
- Sparrow Hospital
- Saint Mary Mercy Hospital
- Mercy Health Mercy Campus
- Lakeland Community Hospital
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- Saint Mary's of Michigan
- Lakeland Hospital
- Marie Yeager Cancer Center
- Munson Medical Center
- Saint John Macomb-Oakland Hospital
- Parkland Health Center-Bonne Terre
- Saint Francis Medical Center
- Southeast Cancer Center
- Capital Region Medical Center-Goldschmidt Cancer Center
- Truman Medical Center
- The University of Kansas Cancer Center-South
- The University of Kansas Cancer Center-North
- The University of Kansas Cancer Center-Lee's Summit
- Phelps County Regional Medical Center
- Saint John's Clinic-Rolla-Cancer and Hematology
- Saint Louis Cancer and Breast Institute-South City
- Missouri Baptist Medical Center
- Mercy Hospital Saint Louis
- Sainte Genevieve County Memorial Hospital
- Cancer Research for the Ozarks NCORP
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Billings Clinic Cancer Center
- Montana Cancer Consortium NCORP
- Saint Vincent Healthcare
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- Cancer and Blood Specialists-Henderson
- Comprehensive Cancer Centers of Nevada - Henderson
- Las Vegas Cancer Center-Henderson
- 21st Century Oncology - Henderson
- Comprehensive Cancer Centers of Nevada-Southeast Henderson
- University Medical Center of Southern Nevada
- Cancer and Blood Specialists-Shadow
- Nevada Cancer Research Foundation CCOP
- Radiation Oncology Centers of Nevada Central
- 21st Century Oncology
- HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
- HealthCare Partners Medical Group Oncology/Hematology-San Martin
- Radiation Oncology Centers of Nevada Southeast
- Cancer Therapy and Integrative Medicine
- Cancer and Blood Specialists-Tenaya
- Comprehensive Cancer Centers of Nevada - Northwest
- HealthCare Partners Medical Group Oncology/Hematology-Tenaya
- Comprehensive Cancer Centers of Nevada-Summerlin
- Las Vegas Cancer Center-Medical Center
- 21st Century Oncology - Fort Apache
- Cancer and Blood Specialists-Fort Apache
- Comprehensive Cancer Centers of Nevada
- HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
- Comprehensive Cancer Centers of Nevada - Central Valley
- 21st Century Oncology - Vegas Tenaya
- University of New Mexico Cancer Center
- Christus Saint Vincent Regional Cancer Center
- Columbia University/Herbert Irving Cancer Center
- University of Rochester
- Cancer Care of Western North Carolina
- Mission Hospital-Memorial Campus
- Asheville Hematology-Oncology Associates
- Southeastern Medical Oncology Center-Clinton
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Iredell Memorial Hospital
- Southeastern Medical Oncology Center-Wilson
- Southeast Clinical Oncology Research (SCOR) Consortium NCORP
- Strecker Cancer Center-Belpre
- Adena Regional Medical Center
- Oncology Hematology Care Inc-Eden Park
- Oncology Hematology Care Inc-Mercy West
- Oncology Hematology Care Inc - Anderson
- Oncology Hematology Care Inc-Kenwood
- Oncology Hematology Care Inc-Blue Ash
- 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
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Samaritan North Health Center
- Dayton NCI Community Oncology Research Program
- Delaware Health Center-Grady Cancer Center
- Delaware Radiation Oncology
- Grady Memorial Hospital
- Oncology Hematology Care Inc-Healthplex
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Fairfield Medical Center
- Marietta Memorial Hospital
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Southern Ohio Medical Center
- Springfield Regional Medical Center
- Upper Valley Medical Center
- Saint Ann's Hospital
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences Center
- Clackamas Radiation Oncology Center
- Providence Milwaukie Hospital
- Providence Newberg Medical Center
- Providence Willamette Falls Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Oregon Health and Science University
- Roper Hospital
- Charleston Hematology Oncology Associates-Roper
- Lowcountry Hematology Oncology PA-North Charleston
- Charleston Hematology Oncology Associates PA-St. Francis
- Lowcountry Hematology Oncology PA-West Ashley
- Greenville Health System Cancer Institute-Easley
- Saint Francis Hospital
- Greenville Health System Cancer Institute-Andrews
- Greenville Health System Cancer Institute-Butternut
- Greenville Health System Cancer Institute-Faris
- Greenville Memorial Hospital
- Greenville Health System Cancer Institute-Eastside
- Greenville Health System Cancer Institute-Greer
- Gibbs Cancer Center-Pelham
- Lowcountry Hematology Oncology PA-Mount Pleasant
- Greenville Health System Cancer Institute-Seneca
- Spartanburg Medical Center
- Greenville Health System Cancer Institute-Spartanburg
- Wellmont Bristol Regional Medical Center
- Wellmont Medical Associates Oncology and Hematology-Johnson City
- Wellmont Holston Valley Hospital and Medical Center
- Wellmont Medical Associates Oncology and Hematology-Kingsport
- The Don and Sybil Harrington Cancer Center
- The Methodist Hospital System
- Huntsman Cancer Institute/University of Utah
- Southwest VA Regional Cancer Center
- PeaceHealth Saint John Medical Center
- Swedish Medical Center-First Hill
- PeaceHealth Southwest Medical Center
- Rocky Mountain Oncology
- Big Horn Basin Cancer Center
- Billings Clinic-Cody
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Trametinib
Chemotherapy
Patients receive trametinib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients receive either A) leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46-48 hours on days 1 and 15 (courses repeat every 28 days); or B) capecitabine PO BID on days 1-14 (courses repeat every 21 days). Patients treated until disease progression or unacceptable toxicity.